vaccines in progress

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.

COLLEGE STATION, Tex. (KBTX/Gray News) - A Texas A&M University professor believes a widely used tuberculosis vaccine could help mitigate the effects of COVID-19, therefore reducing the hospitalization and death rates related to the virus.


Texas A&M Chancellor John Sharp last week offered $2.5 million to make sure the work of Dr. Cirillo can move forward as quickly as possible. (Photo provided by Texas A&M University System)
The Bacillus Calmette-Gu?rin, or BCG, is a vaccine primarily used against tuberculosis. It's also used to treat bladder cancer in the U.S.

As the coronavirus has spread around the world, researchers have noticed that the morbidity and mortality rates were lower in some developing countries where the BCG vaccine is widely used.

Researchers hope to demonstrate that the BCG mitigates the effects of the virus, allowing fewer people to be hospitalized or to die from COVID-19.

Texas A&M is the first U.S. institution in the clinical trial to have federal clearance for testing on humans. Healthcare workers will be the first people eligible for the clinical trial, which is set to begin this week.

"It's not going to prevent people from getting infected," said Jeffrey D. Cirillo, a Regent's Professor of Microbial Pathogenesis and Immunology at the Texas A&M Health Science Center. "This vaccine has the very broad ability to strengthen your immune response. We call it 'trained immunity.'

More “striking” evidence has emerged that the BCG vaccine given to counter TB may provide protection against Covid-19 and significantly reduce death rates in countries with high levels of vaccination.

A study of 178 countries by an Irish medical consultant working with epidemiologists at the University of Texas in Houston shows countries with vaccination programmes – including Ireland – have far fewer coronavirus cases by a factor 10, compared to where BCG programmes are no longer deployed.

This translates into a death rate up to 20-times less, according to urologist Paul Hegarty of the Mater Hospital, Dublin.

Their “correlation” study, expected to be published shortly by PLOS journal, is largely a statistical one and comes with caveats because of possibility of confounding factors. But it is more comprehensive than an initial one conducted in New York, which prompted a scaling up of clinical trials on people with Covid-19.

To reduce the possibility of error, the researchers re-evaluated cases during the course of the pandemic and made country-by-country comparisons including between Ireland and the UK, Mr Hegarty said. “We did not expect to see such a marked difference.”

“Over the 15 days, incidence of Covid-19 was 38 per million in countries with BCG vaccination whereas the incidence of Covid-19 was 358 per million in the absence of such a programme. The death rate was 4.28 per million in countries with BCG programmes and 40 per million in countries without such a programme,” he added.

Scientists conclude people cannot get coronavirus twiceA number of reported cases of coronavirus patients relapsing after overcoming the disease were actually due to testing failures, South Korean scientists say.

Researchers at the South Korean centre for disease control and prevention (CDC) now say it is impossible for the COVID-19 virus to reactivate in human bodies.

There have been more than 10,000 confirmed coronavirus cases in South Korea, with 245 deaths - a 2.3% fatality rate, which is lower than the 3.4% average as stated by the World Health Organisation.

A total of 277 patients in the country were believed to have fallen ill for a second time, as had patients in China and Japan.

This prompted concerns that the virus could be mutating so quickly that people were not necessarily immune to catching it again.

However, genetic analyses of the virus have not found any substantial changes which would effectively disguise it from the immune system.

Partially as a result of these reports, the World Health Organisation warned governments against using so-called "immunity passports" to allow people to return to work simply because they have antibodies for the virus.

Immunity passports are a prop

In 1997, when he and Melinda first ventured into public health … they focused on birth control, funding a Johns Hopkins effort to use computers to help women in the developing world learn about contraception. The logic was crisp and Bill Gates-friendly. Health = resources ÷ people. And since resources, as Gates noted, are relatively fixed, the answer lay in population control.

As further discussed in this piece, Gates later came to the conclusion that birth control was not the best approach to achieve the goal of slower population growth, instead realizing that — counterintuitively — a reduction in childhood mortality was the best way to limit population growth:

In society after society, he saw, when the mortality rate falls—specifically, below 10 deaths per 1,000 people—the birth rate follows, and population growth stabilizes. “It goes against common sense,” Gates says. Most parents don’t choose to have eight children because they want to have big families, it turns out, but because they know many of their children will die.

“If a mother and father know their child is going to live to adulthood, they start to naturally reduce their population size,” says Melinda.

Robert Gallo, MD, the Homer and Martha Gudelsky Professor in Medicine and co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine, appeared on C-SPAN’s “Washington Journal” today, providing insight into COVID-19 treatments.

Gallo, also co-founder and chairman of the International Scientific Leadership Board of the Global Virus Network, appeared for nearly an hour on the C-SPAN program with host Pedra Echevarria, explaining how the novel coronavirus works and potential treatments and research while answering questions from callers.