vaccines in progress

New Delhi: While the link between the Bacillus Calmette-Guérin (BCG) vaccination used to fight tuberculosis and a possibly lowered risk of Covid-19 has been debated since the beginning of the pandemic, US researchers revealed that there are several other vaccines that give some degree of protection from the virus.

According to the researchers, including those from the Mayo Clinic, vaccines for Polio, HIB, MMR, Varicella, PCV13, Geriatric Flu and Hepatitis A–Hepatitis B offer a degree of protection from Covid-19.

HIB works against influenza, MMR against measles-rubella, PCV against pneumococcal infections and varicella against chicken pox.

The study, published in Scientific Reports journal, looked at the efficacy of non-Covid vaccines against the SARS-CoV-2 virus and concluded that polio works the best among them.

“In particular, we find that individuals who have been recently vaccinated with one of Polio, HIB, MMR, Varicella, PCV13, Geriatric Flu, or HepA–HepB vaccines have lower rates of SARS-CoV-2 infection,” the researchers wrote.

They added: “These vaccines are promising candidates for follow-up pre-clinical animal studies and clinical trials in the COVID-19. For the rest of the 18 vaccines that we considered, the correlations with SARS-CoV-2 infection were either insignificant or varied across the time horizons of interest,”

Meanwhile, the preliminary findings of the ACTIVATE trial in Canada revealed that there is a 53 per cent decrease in the incidence of all new Covid-19 infections in people with BCG vaccinations.

The double-blind, placebo-controlled study by the University Health Network, Toronto, is looking at whether vaccination with BCG vaccine would reduce participants’ susceptibility to Covid-19.

Also read: South Asia will see 5 lakh more Covid deaths, over 4.9 lakh will be in India, says UN report

Polio vaccine the most effective
Apart from Covid vaccines, which have shown efficacies in the range of 62 to 94 per cent, and BCG that is under trial, the researchers found that the polio vaccine provides the best protection.

“At the 1 year and 2 year time horizons, the associations of the Polio vaccine to lower rates of SARS-CoV-2 infection are most robust,” they wrote.

The study further argued that the vaccines probably work by activating broad immune signalling pathways — a non-specific innate immune response that is often referred to as “trained” immunity.

However, once a person contracts the disease, these vaccines do not seem to provide any protection either from the need to get hospitalised or even ICU admission.

In another trial by the Bandim Health Project, a health and demographic surveillance system in the African country Guinea-Bissau, investigators are looking at the effect of the oral polio vaccine in 3,400 people aged above 50 years to test the hypothesis that the vaccine reduces the combined risk of morbidity, hospital admission or death (composite outcome) in Covid-19 by at least 28 per cent over six months.

A research team in St Petersburg University, Russia has found a link between countries where the bacille Calmette-Guerin (BCG) vaccine is given on a long-term and regular basis, and the severity of COVID-19 infection and mortality. Analysing some 100 academic papers and published statistics on the incidence of COVID-19 in various countries of the world, the data showed that the spread of the new coronavirus infection occurs more slowly where there is a large percentage of people vaccinated against tuberculosis with the BCG vaccine.

The data analyzed comes from Finland, China, Japan, Korea, and also countries in Eastern Europe, Central and South Asia, Africa, and the former USSR.

"The mortality rate turned out to be lower in those countries and areas where national vaccine immunization programmes have taken place for a long time or continue today, especially if revaccinations were practised," the researchers said in a press release Friday.

The trends observed in the data also suggest that the effect of BCG-linked immunity against COVID-19 comes from early and long-term influence of the vaccine strain on the immune system, i.e., if taken at a young age and in the proper vaccination schedule. This additional 'adjuvant' effect – wherein the response of the immune system is enhanced in a non-specific way – could act against multiple antigens including infectious ones like COVID-19 .

"The causative agent of the new coronavirus infection and BCG have common peptides, which means that induction of cross-immunity is possible," one of the study authors Iana Ivashkevich, a graduate of the online General Pathophysiology program of St Petersburg University, is quoted as saying.

Many clinical trials of the BCG vaccine are underway, and trials of its use for in preventing the new coronavirus infection are being explored under different conditions. The researchers explain that the possibility of BCG vaccination decreasing the transmission and severity of COVID-19 is being actively explored in studies of international research teams from the USA, Germany, Canada, India, and Iran.

While the effect of BCG vaccination in adults is yet to be determined, the researchers said it's possible the vaccine won't be as effective in adults who weren't vaccinated as children.

"There is reason to believe that in adults and elderly people who were not vaccinated in early childhood, the effect of late vaccine administration will be significantly less," explained Dr Leonid Churilov, Deputy Head of the Laboratory of the Mosaic of Autoimmunity and Head of the Department of Pathology at St Petersburg University.

However, there are also contradictory studies that the BCG vaccine was less effective but still reduced the severity of the infection in adults.

"...there are research papers by scientists from the Netherlands, where BCG is not given in childhood. They indicate that BCG administration to adults does not worsen, and, perhaps, somewhat attenuates the course of the disease when infected with the new coronavirus ," Churilov added.

The study review has been published in the academic journal Juvenis scientia.

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A new study published in the journal of the American Society for Microbiology indicates that the mumps IgG titers, or levels of IgG antibody, are inversely correlated with severity in recovered COVID-19 patients previously vaccinated with the measles-mumps-rubella (MMR) vaccine.

Published on November 20, 2020, the researchers in this study found a significant inverse correlation (rs = -0.71, P < 0.001) between mumps titers and COVID-19 severity within the MMR II sub-group.

Within the MMR II group, mumps titers of 134 to 300 AU/ml (n= were only found in those who were functionally immune or asymptomatic.

And those study participants with mild COVID-19 symptoms had mumps titers below 134 AU/ml (n=17). All with moderate symptoms had mumps titers below 75 AU/ml (n=11). All who had been hospitalized and required oxygen had mumps titers below 32 AU/ml (n=5). Titers were measured by Quest Diagnostics using their standard diagnostic protocol.

However, there were no significant correlations between mumps titers and disease severity in the comparison group, between mumps titers and age in the MMR II group, or between severity and measles or rubella titers in either group.

"We found a statistically significant inverse correlation between mumps titer levels and COVID-19 severity in people under age 42 who have had MMR II vaccinations," stated the lead study author Jeffrey E. Gold, president of World Organization, in Watkinsville, Georgia, in a press release.

"This may explain why children have a much lower COVID-19 case rate than adults, as well as a much lower death rate.”

The paper said that while the associations that we have observed between MMR II and COVID-19 do not prove causation, the significant associations lend further support to the theory that the MMR II vaccine may provide long-term, cross-protective immunity against COVID-19.

The majority of children in the USA get their first MMR vaccination around 12 to 15 months of age and a second one from 4 to 6 years of age.

"This is the first immunological study to evaluate the relationship between the MMR II vaccine and COVID-19. The statistically significant inverse correlation between mumps titers and COVID-19 indicates that there is a relationship involved that warrants further investigation," added co-author David J. Hurley, Ph.D., professor, and molecular microbiologist at the University of Georgia.



"The MMR II vaccine is considered a safe vaccine with very few side effects. If it has the ultimate benefit of preventing infection from COVID-19, preventing the spread of COVID-19, reducing the severity of it, or a combination of any or all of those, it is a very high reward low-risk ratio intervention. Maximum seropositivity is achieved through two vaccinations at least 28 days apart.”

Suggestions for further research include randomized controlled clinical trials of MMR II, investigations of anti-mumps antibodies to assess potential effects against SARS-CoV-2, the utilization of larger sample size, and employing more-predictive types of analysis of data to establish a causal link between various levels of immunity offered by MMR II and severity of COVID-19 symptoms.

“Based on our study, it would be prudent to vaccinate those over 40 regardless of whether or not they already have high serum MMR titers,” concluded Dr. Hurley.

A similar study published in The American Journal of Medicine on October 23, 2020, suggested 'the MMR vaccine may protect against COVID-19, including high-risk individuals, such as the elderly with comorbidities, and health care workers and first responders with COVID-19 patients, especially individuals living in long-term care facilities and the related institutional staff.'

Previously, a worldwide study was announced on September 3, 2020, co-led by Washington University, University College London, and the University of the Witwatersrand in Johannesburg, South Africa, plans to determine the MMR's vaccine efficacy against COVID-19. This phase 3 study aims to enroll 30,000 healthcare workers. In some countries where the MMR vaccine isn’t widely given to children, these healthcare workers may be receiving the vaccine for the first time.

The Bacille Calmette-Guerin or BCG vaccine, originally made against tuberculosis, may help in the management of COVID-19, especially in the elderly, says a study by the Indian Council of Medical Research (ICMR). The BCG vaccination is known to induce innate immune memory, which confers protection against several infections, the study uploaded as a preprint at medRxiv, reported. Follow NewsGram on Twitter to stay updated about the World news. “We investigated the impact of BCG vaccination on the frequencies of T cell, B cell, monocyte and dendritic cell subsets,” the study researchers from ICMR wrote. “We also investigated total antibody levels in a group of healthy elderly individuals (age 60-80 years) at one-month post-vaccination as part of our clinical study to examine the effect of BCG on COVID-19,” they added.

The results showed that BCG vaccination induces enhanced innate and adaptive immunity in elderly individuals which may prove beneficial against the coronavirus. BCG vaccine has a general stimulating effect on the immune system and is, therefore, effective against COVID-19. Unsplash “Finally, BCG vaccination resulted in elevated levels of all antibody isotypes,” the researchers wrote. Want to read more in Hindi? Checkout: जानिए क्या है आरोग्य वन, एकता मॉल और पोषक पार्क की खासियत “BCG vaccination was associated with enhanced innate and adaptive memory cell subsets, as well as total antibody levels in elderly individuals,” they concluded. Earlier in October, as part of a large-scale global trial, scientists in Britain launched a study to test if the widely-used BCG vaccine could help protect people against COVID-19.

Industry A study published in the journal ‘Cell Reports Medicine’, also revealed that the BCG vaccine has a general stimulating effect on the immune system and is, therefore, effective against COVID-19. (IANS). Read more at: https://www.newsgram.com/bcg-vaccine-can-help-managing-covid-elderly-icmr/

• [Pre-print, not peer-reviewed] A systematic review of 12 studies found that receiving seasonal influenza vaccination was not associated with greater risk of SARS-CoV-2 infection or disease severity in any studies. Several studies found that influenza vaccination was associated with lower risk of SARS-CoV-2 infection, while others found no relationship (7 studies, 242,323 patients). Similarly, several studies found that influenza vaccination was associated with reduced severity of COVID-19 severity, while others found no relationship (5 studies, 111,820).

Finally, 20 elderly volunteers aged between 60 and 80 years have been administered with the anti-tuberculosis vaccination (TB) — Bacille Calmette-Guérin vaccine (BCG) at the King Edward Memorial (KEM) Hospital.

As part of the trials, which had been approved by the ICMR, an estimated 200 elderly citizens in the age group of 60 to 80, free from COVID-19 or any other ailments, will be inoculated with a dose of BCG vaccine.

“BCG vaccines are given to those volunteers who are healthy and their both RT-PCR and antigen testing turn out to be negative. It is a multi-centric study,” said a doctor.

The BCG vaccine is given when children are young and is expected to last for 40 to 50 years, during which they are expected to develop strong immunity towards tuberculosis, he said. The persons vaccinated in the trial will be first checked after 28 days.

“We will check how they have responded after the inoculation and test them for antibody titer. We will keep checking them over a period of time to see how long the antibody cover is available and how the person responds with the cover,” Suresh Kakani, Additional Municipal Commissioner, BMC.

Often Covid-19 patients develop inflammatory reactions which lead to severity of their infection and even death. In this backdrop, doctors have opined that BCG vaccination, by enhancing innate immune response, may have deleterious effects on coronavirus. “Several researches have shown a correlation that people who received BCG vaccination did not get sick more often or become seriously ill. It has long-lasting effects to boost the immune system. It is believed that despite having such a huge population, Covid-19 fatality rate in India is low because of the BCG vaccine which is given to all children since the early 90s,” said Dr Lalit Anande, medical superintendent of Sewri TB Hospital.

Impact of routine infant BCG vaccination in the young generation on prevention of local Covid-19 spread in Japan” — a study published on August 11 — suggested that BCG vaccination does play an influential role in protecting against the spread of infection on a mass scale. The authors wrote, “Our findings suggest that routine infant BCG vaccination coverage in the young generation had a significant impact on prevention of local Covid-19 spread in Japan.”

MEXICO CITY (Reuters) - Mexico is due to take part in clinical trials of an Italian vaccine being developed against the coronavirus, Foreign Minister Marcelo Ebrard said on Tuesday.

Ebrard did not say when Mexico would begin the trials of the GRAd-COV2 vaccine being carried out by the National Institute for Infectious Diseases 'Lazzaro Spallanzani' in Rome.

"Yesterday they told us," Ebrard told a news conference. "We are very grateful to Italy."

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The Lazzaro Spallanzani institute this week announced it would conduct trials on 90 volunteers over the coming weeks, with the hope a vaccine may be available by spring of next year.

It is not clear if Mexico will take part in phase 2 or the later, and bigger, phase 3 trials of the Italian vaccine being developed by ReiThera, a company based in Rome.

Ebrard said Mexico has signed an agreement for 2,000 volunteers to take place part in trials of Russia's "Sputnik V" vaccine.

Latin America has become a key location for global vaccine trials, with the wide spread of the virus in the community allowing developers to test the efficiency of their vaccines.

Mexico is also preparing to carry out late-stage trials for France's Sanofi, U.S. pharmaceutical giant Johnson & Johnson and two Chinese companies.



(Reporting by Raul Cortes Fernandez; Writing by Drazen Jorgic; Editing by Frank Jack Daniel)

Otazu points to smaller clinical trials that have had exciting results. “The most exciting study is the one in UAE, which would be the most relevant for India, because there is also a BCG mandatory policy in UAE as well. The booster vaccination seemed effective,” he said.

The August 2020 study showed – “71 subjects received the booster vaccination. This group had zero cases of positive COVID-19 infection. 209 subjects did not receive the vaccination, with 18 positive PCR confirmed COVID-19 cases.” This study too is not peer reviewed so far.

Otazu points to another “tantalising” data set from Jordan that was published in July. “For instance, this small study in Jordan shows that more of the asymptomatic people (35 out of 37 or 94.6%) received the BCG vaccination compared to the symptomatic ones (33 out of 44 or 75%),” once again pointing to a need to conduct larger clinical trials to establish the efficacy of the BCG vaccine in controlling the severity of the symptoms of COVID-19.

A recent study conducted in South Africa showed that re-vaccination with BCG in adults reduced the incidence of respiratory infections by 70%.

Currently there are large double blind clinical trials currently underway in Australia, the US, South Africa, Germany, Netherlands, Greece and now in India as well.

Tuberculosis (TB) susceptibility and disease are significantly exacerbated in people with type 2 diabetes. The underlying mechanisms are incompletely understood, and it is not known if new TB vaccine candidates will be safe and provide protection in the context of diabetes. Using a long-term diet-induced murine model of type 2 diabetes, we demonstrate that increased susceptibility to TB is caused by impaired mycobacterial recognition and killing in the diabetic lung. Importantly, we show that mucosal vaccination of diabetic mice with Bacillus Calmette–Guérin (BCG) strains expressing the ESX-1 secretion system from Mycobacterium tuberculosis can overcome this defect and provide superior immunity against TB. Our data warrant a consideration of ESX-1–containing BCG strains as effective TB vaccines in older individuals and diabetics.

Martha Berg and colleagues instead focused on changes in the growth rates of COVID-19 cases and deaths, while controlling for variables including diagnostic test availability, median age, per capita GDP, population size and density, net migration rate, and various cultural differences, such as individualism.

They analyzed the day-by-day rate of increase of confirmed cases in 135 countries and deaths in 134 countries in the first 30-day period of each country's outbreak. Mandatory BCG vaccination correlated with a flattening of the curve in the spread of COVID-19, the analysis showed.

....

This new study was published by Science Advances on July 31, 2020, estimated that very few US residents would likely have died from COVID-19 disease if the USA had instituted mandatory BCG vaccination several decades ago.

Abstract
BCG vaccination may reduce the risk of a range of infectious diseases, and if so, it could serve as a protective factor against COVID-19. Here, we compared countries that mandated BCG vaccination at least until 2000 with countries that did not. To minimize any systematic effects of reporting biases, we analyzed the rate of the day-by-day increase in both confirmed cases (135 countries) and deaths (134 countries) in the first 30-day period of country-wise outbreaks. The 30-day window was adjusted to begin at the country-wise onset of the pandemic. Linear mixed models revealed a significant effect of mandated BCG policies on the growth rate of both cases and deaths after controlling for median age, gross domestic product per capita, population density, population size, net migration rate, and various cultural dimensions (e.g., individualism). Our analysis suggests that mandated BCG vaccination can be effective in the fight against COVID-19.

...Discussion
Our analysis shows that mandatory BCG vaccination is associated with a flattening of the curve in the spread of COVID-19. The effect we demonstrate is quite substantial. For example, our model estimates that the total number of COVID-19 related deaths in the US as of March 29, 2020 would have been 468—19% of the actual figure. (2467)—if the US had instituted the mandatory BCG vaccination several decades earlier (see Supplementary Analysis 5).

...

6 MINUTE READ
BY AMY MCKEEVER

PUBLISHED JULY 31, 2020

More than 150 coronavirus vaccines are in development across the world—and hopes are high to bring one to market in record time to ease the global crisis. Several efforts are underway to help make that possible, including the U.S. government’s Operation Warp Speed initiative, which has pledged $10 billion and aims to develop and deliver 300 million doses of a safe, effective coronavirus vaccine by January 2021. The World Health Organization is also coordinating global efforts to develop a vaccine, with an eye toward delivering two billion doses by the end of 2021.

Jharkhand: Adar Poonawalla, the CEO of Serum Institute of India, has said that his company plans to make millions of doses of COVID-19 Vaccine in a period of over three months, The Indian Express reported.

Serum Institute of India Pvt Ltd is the world’s largest vaccine manufacturer and has partnered with AstraZeneca, a British-Swedish company to manufacture the vaccine.

Clivea
Poonawalla has said that it will take a long time before everyone gets a vaccine that would be the best alternative of all the possible vaccines in line for treating COVID-19.

Serum Institute has invested hundreds of millions of dollars with AstraZeneca to come up with a suitable vaccine, the announcement of which will be made in a few days. According to The Indian Express report, AstraZeneca’s vaccine has already conducted phase 1 tests.

Poonawlla also hinted that after getting the manufacturing license for the vaccine, his company will produce the same in large quantities. Moreover, the company has also committed millions of dollars in Capex and Opex to produce the vaccine.

About the company’s TB vaccine, VPM BCG, Poonawalla said that the vaccine has already been tested on more than 1000 patients. In two months’ time it will be known whether the vaccine reduces the severity of coronavirus or not.

The government said the trials will be conducted at the National Institute for Research in Tuberculosis (NIRT) in this metropolis and sanction for the same has been accorded. The Tamil Nadu government’s announcements comes on the heels of independen...studies suggesting that the BCG vaccine, which is widely used in countries like India as part of their fight against tuberculosis (TB), is found to be effective in reducing the incidence of Covid-19 and the mortality rate

The BCG vaccine has been an integral part of India’s immunisation programmee for the past several decades. Health Minister C Vijayabhaskar said the BCG vaccine is found to be playing a role in increasing innate immunity and there are chances of reducing morbidity and mortality if the vaccine is administered to people in the age of 60 to 95 years.

Those administered the vaccine will remain under observation for 180 days

Putting life into a much talked about theory, two independent studies including one carried out by researchers at Jawaharlal Nehru University, here have shown that countries with an active Bacillus Calmette-Guérin vaccination programme have much redu...

The COVID-19 pandemic is one of the most devastating in recent history. The bacillus Calmette−Guérin (BCG) vaccine against tuberculosis also confers broad protection against other infectious diseases, and it has been proposed that it could reduce the severity of COVID-19. This epidemiological study assessed the global linkage between BCG vaccination and COVID-19 mortality. Signals of BCG vaccination effect on COVID-19 mortality are influenced by social, economic, and demographic differences between countries. After mitigating multiple confounding factors, several significant associations between BCG vaccination and reduced COVID-19 deaths were observed. This study highlights the need for mechanistic studies behind the effect of BCG vaccination on COVID-19, and for clinical evaluation of the effectiveness of BCG vaccination to protect from severe COVID-19.

Writing in their paper, they say: 'This epidemiological study assessed the global linkage between BCG vaccination and Covid-19 mortality.

'Signals of BCG vaccination effect on Covid-19 mortality are influenced by social, economic, and demographic differences between countries.

'After mitigating multiple confounding factors, several significant associations between BCG vaccination and reduced Covid-19 deaths were observed.'

The BCG vaccine was invented a century ago and gives immunity to tuberculosis (TB) — a bacterial infection — but it is known to have other benefits.

Previous trials discovered people who receive the jab, which costs as little as £30, have improved immune systems and are able to protect themselves from infection.

For example, in a trial among Native Americans, BCG vaccination in childhood was able to offer protection against TB up to 60 years after vaccination.

These so-called off-target effects include enhanced protection against respiratory diseases, and have been recognised by the World Health Organization (WHO).

BCG has been used for more than 90 years but exactly how it works still remains a mystery.

And how it may protect against Covid-19 is an even larger enigma.

The best theory is that the vaccine, which contains a live bacteria called Mycobacterium, boosts the innate immune system, making it more effective.

Ongoing studies into whether BCG can help fend of Covid-19 are ongoing in Holland and Australia but, until these results are available, the researchers of the latest study say even transient immunity could help fight the pandemic.

'[The BCG vaccine] may be useful in individuals at high risk, such as health workers, first responders, and police officers, or those with preexisting conditions such as obesity, diabetes, or cardiovascular disease,' say researchers.

'Similarly, even enhanced unspecific immunity through BCG vaccination in vulnerable age groups could ameliorate severe Covid-19.

'Temporarily induced trained immunity could buy time until specific vaccines and/or effective treatments against SARS-CoV-2 infections become available.'

How useful this short-term immunity would be in the current pandemic, remains to be seen.

Professor Ben Neuman, Visiting Associate Professor at the University of Reading, say that while there is a clear benefit to using BCG to protect against TB, 'it is questionable whether a tuberculosis vaccine would be seen as a viable form of long-term immune system modification for use against Covid-19'.

"In our initial research, we found that countries with high rates of BCG vaccinations had lower rates of mortality," explained Escobar, a faculty member in the Department of Fish and Wildlife Conservation and an affiliate of the Global Change Center housed in the Fralin Life Sciences Institute. "But all countries are different: Guatemala has a younger population than, say, Italy, so we had to make adjustments to the data to accommodate those differences."

Escobar, working with NIH researchers Alvaro Molina-Cruz and Carolina Barillas-Mury, collected coronavirus mortality data from around the world. From that data, the team adjusted for variables, such as income, access to education and health services, population size and densities, and age distribution. Through all of the variables, a correlation held showing that countries with higher rates of BCG vaccinations had lower peak mortality rates from COVID-19.

One sample that stood out was Germany, which had different vaccine plans prior to the country's unification in 1990. While West Germany provided BCG vaccines to infants from 1961 to 1998, East Germany started their BCG vaccinations a decade earlier, but stopped in 1975. This means that older Germans -- the population most at risk from COVID-19 -- in the country's eastern states would have more protection from the current pandemic than their peers in western German states. Recent data shows this to be the case: western German states have experienced mortality rates that are 2.9 times higher than those in eastern Germany.

Intra-vesical Bacillus Calmette-Guérin (BCG) immunotherapy is an effective treatment for high-risk bladder cancer. Less well known is that fewer than 1% of patients receiving BCG treatment can develop disseminated BCG. The reaction can range from a mild flu-like illness to a systemic disorder with a fulminant course which in the most severe cases can lead to death. The diagnostic yield is low and diagnosis is often made after a comprehensive exclusion of more common causes of pyrexia of unknown origin. A high level of suspicion is therefore required in those who may be at risk. We report a case of disseminated BCG in an older patient for whom early involvement of his family was pertinent to determining the precipitant for delirium.

The journal of the Royal College of Physicians of Edinburgh. 2020 Jun [Epub]

John Headlam, Alice Wheeler, Keith Yuen, Elizabeth Brierley, Oliver M Todd

BCG:CoVac vaccine candidate combines the BCG vaccine with components of the SARS-CoV-2 virus

June 22, 2020 -- Could live vaccines for viruses such as measles, mumps, and rubella (MMR) also provide protection against COVID-19? That intriguing prospect is the subject of a recently published commentary in mBio.

There is mounting evidence that live attenuated vaccines, such as the MMR vaccine, provide protection against lethal infections unrelated to the pathogen that was originally targeted. The proposed mechanism for this protection is "trained innate immunity," by which leukocyte precursors in the bone marrow are "trained" by the vaccine to function more effectively against broader infectious insults. The protection is mediated by long-lived myeloid-derived suppressor cells (MDSCs), cells that previously have been reported to inhibit septic inflammation and mortality.

Now, induction of MDSCs is thought to inhibit or reduce severe lung inflammation or sepsis associated with severe COVID-19 infection. Researchers from Louisiana State University and Tulane University demonstrated that vaccination with a live attenuated fungal strain induces trained innate protection against lethal polymicrobial sepsis. They also cited six clinical trials in other countries that are testing trained innate immunity with the live attenuated tuberculosis Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine. Other childhood vaccines, including those for rotovirus, smallpox, and chickenpox, may work in a similar manner to limit inflammation and sepsis.

"Live attenuated vaccines seemingly have some nonspecific benefits as well as immunity to the target pathogen. A clinical trial with MMR in high-risk populations may provide a low-risk/high-reward preventive measure in saving lives during the COVID-19 pandemic," said Paul Fidel, PhD, department chair of oral and craniofacial biology at Louisiana State University (LSU) and associate dean for research at the LSU Health School of Dentistry.

The "trained innate immunity" hypothesis may explain why children have been less likely to be impacted by COVID-19, since they have more recent and frequent exposures to live attenuated vaccines that may induce trained suppressive MDSCs that limit inflammation and sepsis. It may also explain why only mild symptoms were observed in the 955 sailors on the USS Roosevelt aircraft carrier who tested positive for COVID-19 in April, with only one hospitalization required. As a precautionary measure, MMR vaccinations are given to all U.S. Navy recruits.

"If adults got the MMR as a child they likely still have some level of antibodies against measles, mumps, and rubella, but probably not the myeloid-derived suppressor cells," said Fidel. "While the MDSCs are long-lived, they are not life-long cells. So, a booster MMR would enhance the antibodies to measles, mumps, and rubella and reinitiate the MDSCs."

Given that there are no contraindications to MMR vaccination of immunocompetent individuals, the authors recommended clinical trials with MMR as a low-risk, high-reward preventive measure for high-risk populations such as healthcare workers who can easily be exposed to COVID-19.

A tuberculosis vaccine developed 100 years ago also makes vaccinated persons less susceptible to other infections. While this effect has been recognized for a long time, it is not known what causes it. Together with colleagues from Australia and Denmark, researchers from Radboud university medical center the universities of Nijmegen and Bonn have now presented a possible answer to this question. Their results are also interesting against the background of the Covid-19 pandemic: several studies are currently testing the use of the vaccine in preventing severe disease progression in populations at risk such as hospital staff and elderly individuals. The study is published in the journal "Cell Host & Microbe".

Prophylactic vaccination is the most effective intervention to protect against infectious diseases. The commonly accepted paradigm is that immunization with both attenuated virus (live but with substantially reduced virulence) and inactivated (killed virus particles) vaccines induces adaptive and generally long-term and specific immunity in the form of neutralizing antibodies and/or activating pathogen-specific cellular immune responses. However, an increasing body of evidence suggests that live attenuated vaccines can also induce broader protection against unrelated pathogens likely by inducing interferon and other innate immunity mechanisms that are yet to be identified. The stimulation of innate immunity by live attenuated vaccines in general, and oral poliovirus vaccine (OPV) in particular, could provide temporary protection against coronavirus disease 2019 (COVID-19).

Professor David Levine from the University of California, Berkeley, says a study of people in Spain and Italy has provided a “shred of evidence” that the BCG vaccination may protect against coronavirus disease 2019 (COVID-19).

The analysis found that among people born when Spain had a program for universal BCG vaccination, rates of confirmed cases of COVID-19 and deaths were slightly lower compared with among people in Italy where no such universal BCG program was ever introduced.

Levine hopes the findings will encourage analysts to access more detailed data covering more outcomes by age and larger sample size to help provide more reliable data.

A pre-print version of the paper can be accessed on the server medRxiv*, while the article undergoes peer review.

Several countries, including Australia, are investigating the link between the BCG vaccine against tuberculosis (TB) and the milder spread of the virus, János Szlávik of the Budapest South Pest Hospital told pro-govt public news channel M1. Hungary, too is conducting a test that involves readministering the BCG shot to health-care workers to see if they are better protected against coronavirus, he said.


However, since the epidemic is winding down in Hungary, it is unclear if the experiment will yield conclusive results, Szlávik said, adding, at the same time, that the answer to the question would likely become clear during a potential second wave of the virus.

Conclusion: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.

the tuberculosis vaccine, BCG, could it protect the Covid-19 ? Five hundred caregivers from south africa started this week in Cape town to test the potential protective effects against the Covid-19 of the good old-used vaccine for more than a century to protect against tuberculosis (BCG). The trial has focused primarily on the health workers, because they are the most exposed to the virus. The results will be made public if they are sufficiently positive. Read also Covid-19 : Africa, you said mystery ? Tests " The clinical trial has begun ", said to AFP, Duncan McDonald, one of the leaders of the organization of medical research TASK that leads to the experience. This test – 250 caregivers will receive an injection of BCG and other 250 a placebo – is conducted in a hospital in the Cape town region under the direction of professor Andreas Diacon, the boss of a TASK. "Some observations suggest that the BCG has effects on the immune system that we don't yet understand completely, especially as it strengthens against respiratory infections," said professor Diacon. studies have proven that children immunized with BCG vaccine suffered less from respiratory diseases. Other work suggests that it may protect against asthma and autoimmune diseases such as type 1 diabetes. Scientists seek to prove he could have similar beneficial effects against the sars coronavirus. "If it was possible to reduce just a little the symptoms of this epidemic Covid-19, this would increase the chances of survival, avoid hospitalizations, and even to get sick ", has been hoped for by the Pr Andreas Diacon. While the global interest in the effects of BCG and its potential for use against Covid-19 has recently gained momentum, the WHO has pointed out that due to a lack of clinical trials, there was no evidence that it provides protection against the virus. "There is experimental evidence in both animal and human studies the BCG vaccine has non-specific effects on the immune system. These effects have not been well characterized and their clinical relevance is unknown, " said the WHO in a press release last month. At the time, WHO said that BCG should not be used against the Covid-19, at the risk of reducing the availability of the vaccination neonatal in countries where tuberculosis is high. "The BCG vaccination prevents severe forms of tb among children and the diversion of supplies to local may result in the non-vaccination of new-born, leading to an increase in diseases and deaths due to tb," said WHO. caregivers in first line In the meantime, the clinical study of Cape town focuses on caregivers, " because we believe that they are the most vulnerable ", he added. The study team will carry out regular statistical tests to see if an advantage of BCG revaccination may be shown. An independent committee will review the results. "If there is a signal strong enough and positive, the results will be made public. " Some 300,000 people – one of the highest rates in the world – are infected each year tuberculosis in South Africa, according to the world health Organization (WHO). All newborns are vaccinated with BCG vaccine, but the disease has made about 63, 000 deaths in 2018. Clinical studies equivalent to that of the Cap are currently conducted in the netherlands, Australia and France to demonstrate a possible effect shield of the BCG. In the United States, a research group in Boston, hopes to test the vaccine in health care workers on the front line in the same purpose. Their results have not been published yet. Invented in France, at the institut Pasteur, it has been almost 100 years by Calmette and Guerin (who have given him their name : vaccine bilié Calmette-Guérin, or BCG), it was administered to 3 billion people in the world, which makes it the most vaccine widely administered. Read also Covid-19 – " vaccines in Africa ? A highly political subject ! " writing will advise you Coronavirus: the vaccine for tuberculosis, possible shield for caregivers Covid-19 : soon to be trials of the vaccine in the DRC ? The soldiers of the Institut Pasteur on the front of the epidemic Coronavirus : three vaccine projects in phase-test on the man Didier Raoult, at the crossroads of Africa and of the science Covid-19 – " vaccines in Africa ? A highly political subject ! "

keep reading ==> https://www.indonewyork.com/technology/Covid-19-South-africa-on-the-trail-of-the-BCG-The-Point-h7187.html

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Biographies:
Paul K. Hegarty, MB, BCh, BAO, FRCSI, FRCS (Urol), Consultant Urologic Surgeon at Mater Private Hospital, Department of Urology, Mater Misericordiae University Hospital, Dublin, Ireland
Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
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Read the Full Video Transcript
Alicia Morgans: Hi, this is Alicia Morgans, Associate Professor of Medicine and GU medical oncologist at Northwestern University in Chicago, Illinois in the United States and I'm so excited to have here with me today Mr. Paul Hegarty, who is a urologic oncologist, a consultant and your urologic surgeon at the Mater Misericordiae in Dublin, Ireland. Thank you so much for being here with me today.

Paul Hegarty: Thank you for having me.

Alicia Morgans: Wonderful. So, Paul, you have been working with several collaborators to come up with a really exciting and interesting study that evaluates BCG vaccination in the setting of SARS-COV 2 really an attempt to vaccinate against it. And I'm wondering if you could tell us a little bit about the background, where this idea came from and why it should work and then we can talk about what that trial entails.

In a growing list of global trials on the efficacy of tuberculosis vaccines in preventing Covid-19, one is an upcoming 10-month trial being conducted by the Indian Council of Medical Research (ICMR) on the BCG vaccine.

What is the BCG vaccine?
Short for Bacillus Calmette-Guérin, BCG is a vaccine that uses a live attenuated strain (potency of the pathogen artificially disabled, but identifying characters retained) derived from an isolate of Mycobacterium Bovis. It has been used across the world, including in India for decades, against tuberculosis.

India, like many other Asian, African, and Latin American countries, has a current national BCG vaccination policy for all at birth. Countries that have terminated their policies or only recommend the vaccine for specific groups are mostly in Europe and North America.


In India, 91.9 per cent of children between the ages of 12 and 23 months have received the vaccine, according to the National Family Health Survey. Outside of some Northeastern states, almost all states have above a 90% BCG vaccination rate. According to the National Health Profile, India has a production capacity of 2,800 lakh BCG vaccine doses.

What will ICMR’s upcoming study on BCG vaccine look at?
It will focus on the vaccine’s potential in reducing the chance of Covid-19 death among those who are above age 60. With new finalised details of this study, results could be seen as early as March 2021, said lead ICMR scientist Suman Kanungo.

The study will cover 1,450 elderly people in six red and orange zones: King Edward Memorial (KEM) Hospital, Mumbai; All India Institute of Medical Sciences (AIIMS), New Delhi; National Institute for Research in Tuberculosis (NIRT), Chennai; National Institute of Occupational Health (NIOH), Ahmedabad; National Institute in Environmental Health (NIREH), Bhopal; and National Institute for Implementation Research on Non-Communicable Diseases (NIIRNCD), Jodhpur.

CAPE TOWN (Reuters) - The idea of testing the BCG vaccine in Africa against COVID-19 was bound to cause controversy, yet officials say efforts underway could, if successful, give the continent a cheap and easily deployable weapon against the virus.

South African biotech group TASK this month started the continent’s first trial to see whether 250 high-risk workers given a booster dose of BCG vaccine show better protection against COVID-19 than the same number given a placebo.

Three thousand health workers are eventually expected to be involved in the trial overall. Researchers expect preliminary results within six months in the year-long trial.

Tests to see if the century-old Bacille Calmette-Guerin (BCG) vaccine, widely used in Africa for tuberculosis, protects against the new coronavirus have also begun in the Netherlands and Australia.

But unlike those countries, where BCG vaccinations at birth aren’t the norm, South Africa’s trial involves injecting people for a second time. BCG injections are mandatory at birth in South Africa, where TB is a leading killer.

“We are trying to see if ... reminding the immune system of that vaccine will make a difference,” said Andreas Diacon, a professor at Stellenbosch University’s medical school who founded TASK in 2005 to hunt for novelty medicines and vaccines.

“Perhaps it works, perhaps it doesn’t, but it’s definitely worth trying ... (because) we just need to know if it can help us through this COVID-19 crisis,” he told Reuters at TASK’s high-security mycobacteriology laboratory.

Trying out a new medical intervention in Africa always rings alarm bells because of an unfortunate history of big pharmaceutical companies using Africans as guinea pigs.

So when a French doctor last month suggested that the BCG should also be tested in Africa as a possible shield against COVID-19, it provoked a predictable social media backlash.

Yet the vaccine is widely regarded as safe, and officials involved in the trial at Tygerberg hospital in Cape Town point out that it is so readily available in Africa and the developing world that poor countries with limited health resources could benefit massively from the discovery that the jab is effective.

“If you look at BCG as a potentially cheap and available tool that African countries could afford ... it does make sense,” Diacon said. “The results will be relevant for ... parts of the world that do not have access to first world medicine.”

The World Health Organization has warned that the next epicentre of the pandemic could very well be Africa, where measures to contain it are harder to implement and health services much more likely to be overwhelmed than in the West.

Slideshow (3 Images)
Across Africa, there is less than one intensive care bed and one ventilator per 100,000 people, a Reuters survey found. The continent has around 85,329 confirmed coronavirus cases and 2,784 deaths, compared with 300,000 worldwide since the virus emerged from China late last year.

There is no known cure for COVID-19 and scientists worldwide are scrambling for vaccine candidates.

“Our experts have ensured stringent ... criteria for trial participants, as well as all the requisite safety and efficacy monitoring measures during the trial,” said a spokesman for the South African Health Products Regulatory Authority.  


 
South Africa BCG booster trials seek low-cost weapon against COVID-19

TORONTO (Reuters) - China's CanSino Biologics Inc, the company behind one of the few coronavirus vaccine candidates already in clinical trials, is collaborating with Canada's National Research Council to "pave the way" for future trials in Canada, the research council said on Tuesday.

The NRC said it would scale up a production process for CanSino's vaccine at a government facility in Montreal, and that CanSino was preparing a trial application for drug regulator Health Canada.

If CanSino's vaccine works, the collaboration could help ensure that Canadians have access to it. Local trial data could reassure Health Canada that the vaccine is safe, and local manufacturing could ensure some doses are at hand.

Asked whether the collaboration would make it possible for Health Canada to consider data gathered in China, NRC said that in general, data can be shared with the regulator's approval.

"Canadian clinical trials will expand on Chinese data and provide an enhanced understanding of the vaccine candidate's safety profile," the agency said.

A vaccine that protects people from the coronavirus could end the pandemic, but finding one that works and manufacturing enough doses is a huge challenge.

The tuberculosis vaccine called Bacille Calmette-Guerin (BCG) has been around since the beginning of the last century. It is the only approved vaccine againsttuberculosis. To date, more than 4 million doses of it have been administered. The new VPM1002 is based on that vaccine.

Scientists at Germany's Max Planck Institute for Infection Biology have developed the vaccine by genetically modifying BCG. Once the vaccine has successfully completed clinical testing, there are plans to use it against tuberculosis worldwide within the next few years.

Infection biologist Stefan Kaufmann was in charge of the development of VPM1002. Now, scientists are also testing the vaccine for its efficacy against COVID-19. Its precursor has already proven to be effective against other infections.

Portrait of Stefan H.E. Kaufmann, Max Planck Institute for Infection Biology
The infection biologist Stefan Kaufmann hopes that the vaccination will strengthen basic immunity against lung diseases

"In controlled studies, it has been shown that BCG can indeed protect against viral respiratory infections. BCG stimulates innate immunity, and this can be used to build a defense against viral respiratory infections. Based on this, we know that our new vaccine should have a similar effect," Kaufmann told DW.

This also gives hope with regard to COVID-19.

VPM1002 strengthens the immune system

Studies in mice show that VPM1002 activates the immune system and could thus significantly attenuate viral infections such as COVID-19.

A vaccine — or a pathogen, for that matter — always stimulates two types of defense by the body. One of these is innate or non-specific immunity. It can kill pathogens very quickly. The other is acquired or specific immunity.

"The interaction between these two immunities ensures the best possible immune response and the best possible endogenous defense," Kaufmann explains.

Microscopic picture of Mycobacterium tuberculosis
VPM1002 will play an important role, especially in the fight against the Mycobacterium tuberculosis

First hurdle overcome

ThePaul Ehrlich Institute has already approved the phase III clinical trial for VPM1002 against COVID-19. It is being conducted at various German hospitals, including the Hannover Medical School (MHH).

As of the beginning of May, scientists have been testing whether the new tuberculosis vaccine activates the immune system in a non-specific way.

"This should help to alleviate the severe progression of respiratory diseases such as COVID-19," Jacobus Bosch tells DW. He is one of the scientists in the team headed by Professor Christoph Schindler, who is lead author of the study. It focuses on the vaccine's effect as a possible agent against COVID-19.

"The new tuberculosis vaccine VPM 1002 will be tested in Hanover exclusively for its efficacy in the current SARS-CoV-2 pandemic situation," says Bosch.

The first nationwide study involves 1,000 test persons. They all work in the medical field and are therefore particularly exposed to a possible infection.

"In a further study, we plan to investigate the efficacy of the improved tuberculosis vaccine VPM1002 in people over the age of 60. The question here is whether VPM1002 can effectively protect this age group, which is currently particularly at risk," the study's director, Schindler, explains.

The second study will involve 2,000 volunteers from all over Germany

VPM1002 as bridging technology

Even if the test results with VPM1002 are positive, Stefan Kaufmann says, further research on a special coronavirus vaccine is still necessary. But if its effects are successful enough, VPM1002 could be produced in large quantities within a short period of time, thus bridging the time until an effective COVID-19 vaccine is found.

"We're not talking about millions, but about 10 to 100 million doses in a short time. This is also very important, because the tuberculosis vaccine BCG is quite scarce, and the World Health Organization is now concerned that infants in countries with TB will not be able to be vaccinated," Kaufmann says.

India is the most likely production location. The Serum Institute of India has been licensed to produce the VPM1002 vaccine. The company is the largest vaccine manufacturer in the world and already has facilities ready for production.

The Bacille Calmette-Guerin (BCG) vaccine is a century-old vaccine that was developed to treat tuberculosis.

ICMR’s head of epidemiology and communicable disease Dr R.R. Gangakhedkar had on 17 April announced clinical trials of the vaccine for Covid-19 prevention, after similar trials were held in the Netherlands, US, Australia and Germany.

The Council of Science and Industrial Research also announced that it would begin clinical trials on the anti-leprosy vaccine called Mycobacterium indicus pranii or MIP, which is a stronger strain of the BCG and is touted as its cousin.

An international research team has identified the mechanism behind one of science's most enduring mysteries: what makes the 100-year-old tuberculosis (TB) vaccine so effective at preventing newborn deaths from diseases other than TB?


The ability of Bacillus Calmette-Guérin (BCG)—one of the oldest, safest and cheapest vaccines available—to provide protection to newborns beyond its intended purpose of fighting off TB has been known since at least the 1940s, but until now no one has been able to explain why or show how it works.

In a new study, published today in Science Translational Medicine, researchers reveal how they identified a dramatic and rapid increase in neutrophils—white blood cells that patrol the body and destroy invading bacterial pathogens—in mice and babies within three days of BCG vaccination.

The drug, developed by U.S. pharmaceutical company, Gilead, will be trialled in five hospitals across Australia just as Dr Anthony Fauci, the U.S.'s authority on coronavirus, lauded the preliminary results of a trial indicating remdesivir had shortened the recovery time of patients.

According to The Guardian, Sydney's St Vincent hospital is the only confirmed location so far with the remaining four still being finalised.

The U.S. trial Dr Fauci referenced was conducted by National Institute of Allergy and Infectious Diseases (NIAID), which has yet to be published or peer-reviewed. Preliminary results have found that patients who used the drug recovered four days faster compared with patients who used a placebo — an improvement of 31 per cent. There was also a slight decrease in the death rate from 11.6 per cent to eight per cent.

The drug was originally designed to help fight Ebola but has since been refocused to treat coronavirus. It works by blocking an enzyme called a polymerase, which effectively stops the virus from multiplying, limiting the development of symptoms and halting further spread.While the NIAID trial's preliminary results have sparked hope across the globe, the results of others using the drug have not been as positive.

A Chinese study published in the Lancet could not find any benefits for the drug, though it admitted it had not reached the expected amount of participants as cases fell considerably in Wuhan by mid-March.

The remdesivir trials will join a number of other vaccine and treatment candidates ongoing around the country.

The CSIRO is testing out two vaccine candidates — one from the University of Oxford, the other from U.S. pharmaceutical company Inovio — while 4,000 healthcare workers around Australia are undertaking trials using the Bacillus Calmette–Guérin (BCG) vaccine usually used for tuberculosis.

The University of Queensland has also been trialling a vaccine, developed by Dutch company Viroclinics Xplore, and has said the results so far have been promising.

The hope is that one of these will prove effective in the coming months.

Ravinder Saini
Tribune News Service
Rohtak, April 30

The Pt BD Sharma Post Graduate Institute of Medical Sciences (PGIMS) will begin clinical trials from Friday to test the use of tuberculosis vaccine BCG (Bacillus Calmette-Guerin) to ward off Covid-19.

Fighting the virus

The BCG vaccine contains a live but weakened strain of TB bacteria that provokes the body to develop antibodies to attack the bacteria.

The trials will be done on 175 attendants of Covid patients, including close contacts, doctors, nurses, ward boys and sanitary workers. They will be administered the BCG vaccine and kept under observation for the next 180 days to find out its effect.

Boosting immunity

Unlike other vaccines, the BCG vaccine also boosts the innate immune system

The BCG vaccine — introduced in the 1920s to fight TB — is currently administered to newborn children. Dr Dhruv Choudhry, investigator of the research and head of Pulmonary Medicine at PGIMS, said the BCG vaccine was known to enhance immunity. “The study aims to explore whether or not persons given the BCG vaccine catch coronavirus infection,” he said.

Dr Savita Verma, another investigator, said consent would be taken from Covid patients’ attendants to be involved in the study. Thereafter, their samples would be collected. “They would be administered BCG vaccine if they test negative for Covid,” she said.