Singapore scientists pursue booster vaccine to counter Covid-19 variants, other coronaviruses

[Mista]

Singapore scientists pursue booster vaccine to counter Covid-19 variants

A study found that Sars survivors fully vaccinated with Pfizer-BioNTech developed antibodies that could neutralise variants and other coronaviruses that could be contracted by humans.

www.scmp.com

• A study found that Sars survivors fully vaccinated with Pfizer-BioNTech developed antibodies that could neutralise variants and other coronaviruses that could be contracted by humans
• Scientists say this could be the basis of a booster vaccine to control the current pandemic and prevent the next one, and want to recruit more Sars survivors for their research

Findings from a study involving survivors of Sars who received two shots of the Pfizer-BioNTech inoculation have raised hopes of what researchers say is a potential “dream vaccine” that can counter Covid-19, its variants and future coronaviruses that jump from animals to humans. Scientists from the Duke-NUS Medical School in Singapore and the government’s National Centre for Infectious Diseases (NCID) found that when people who had recovered from Sars (severe acute respiratory syndrome) were fully vaccinated with the Pfizer-BioNTech jab, they developed high levels of antibodies that could neutralise all known Covid-19 variants of concern as well as other coronaviruses circulating in animals that could potentially be contracted by humans.

Professor Wang Linfa from the Duke-NUS emerging infectious diseases programme, one of the study’s authors, said the findings were key for the development of next-generation vaccines that would not only help with controlling the current pandemic “but may also prevent or reduce the risk of future pandemics caused by related viruses”.

Before receiving Covid-19 vaccinations, the Sars survivors only had antibodies against the disease they recovered from. The Sars-CoV-1 virus that causes Sars shares an overall genome sequence identity of almost 80 per cent with the Sars-CoV-2 virus causing the Covid-19 disease.

Wang said the “eureka moment” during the study came when those who had recovered from Sars and were jabbed with the Pfizer vaccine showed uniform high-level cross-neutralising antibodies against 10 different sarbecoviruses. These are a subgroup of coronaviruses – including the ones that caused Sars and Covid-19 – with the potential to jump from animals to humans and potentially start the next pandemic.

By comparison, those who had never been ill with Sars or Covid-19 and were vaccinated against the latter showed antibodies against the virus that causes Sars, but the levels were “not good enough”, Wang said. Those who recovered from Covid-19 had higher levels of antibodies after getting jabbed than those who had not contracted either disease, but their Sars antibodies were still not very high.

The study, published in the influential New England Journal of Medicine on August 18, was conducted this year with 28 people – eight Sars survivors, 10 healthy people who had not contracted Sars or Covid-19, and 10 who had recovered from Covid-19.

The immune responses of all 28 were compared before and after they received two doses of the Pfizer-BioNTech vaccine, which uses Messenger RNA (mRNA) technology to provide human cells with the genetic instructions to make a harmless surface protein of Covid-19. This protein then trains the immune system to recognise and build a response against the actual virus.

Covid-19 was first identified in the Chinese city of Wuhan in late 2019, but scientists have not yet been able to identify the source of the virus or how it spread, which could help them prevent a future coronavirus-fuelled pandemic.

Wang from Duke-NUS and the team of researchers across medical schools and hospitals in Singapore have a name for the potential third-generation vaccine: 3GCoVax.

The current first-generation vaccines offer varying levels of protection against Covid-19, but their efficacy is lower against new variants of the virus, especially the highly contagious Delta variant.

Several second-generation vaccines that can protect against the original strain, current variants and other human-infective coronaviruses are being developed. Scientists are also concerned that new, deadlier variants will emerge that could render current vaccines ineffective.

Said Wang: “I think it’s the first time in the history of mankind that – if everything goes according to the World Health Organization’s plans – by this time next year, the majority of the global population will be vaccinated against Sars-CoV-2. So if we boost that population with 3GCoVax, we also potentially can be ready to fight and prevent the next pandemic.”

He added that there were already “several companies at the contract stage” who were interested in building on these findings to make such a booster vaccine.

Wang – one of the world’s leading experts in zoonotic diseases, bat immunology and pathogen discovery – said the team was also keen to create broad neutralising antibodies for therapy, apart from developing 3GCoVax.

They are looking to recruit more people who have recovered from Sars, as he is hopeful that Sars survivors will also show the same antibody response after receiving vaccines made by AstraZeneca or Sinovac.

Wang said he was keen to study those in mainland China, Hong Kong and Canada, where there were larger cohorts of Sars survivors.

The Sars epidemic of 2003 infected more than 8,000 people around the world, resulting in at least 774 deaths. Hong Kong was badly hit, with a total of 1,755 cases and 299 deaths; mainland China had 5,327 cases and 343 deaths; while Canada had 438 cases and 44 deaths.

“My hypothesis is that [the other vaccines will produce the same effect with Sars survivors]. But as a scientist, you know, you don’t trust your hypothesis only, you need the real data,” he said.

Those who would like to take part in ongoing studies can contact the researchers at
scrn@ncid.sg.

 

[Mista]

Decades-old SARS virus infection triggers potent response to COVID vaccines

Dramatic antibody production in people infected during the 2002–04 outbreak furthers hopes of a vaccine against many coronaviruses.

www.nature.com

 

[Yongpeng Sun-Tastaufen]

No one ever made a coronavirus vaccine before 2020 because no one cared enough to do it because symptom is mild. On the other hand, flu shot has been around for decades to battle influenza.

 

[Mista]

Science | AAAS

www.sciencemag.org

COVID-19 vaccines may trigger superimmunity in people who had SARS long ago


Almost 20 years before SARS-CoV-2, a related and even more lethal coronavirus sowed panic, killing nearly 10% of the 8000 people who became infected. But the 2003 outbreak of severe acute respiratory syndrome (SARS) may have left some survivors with a gift. Former SARS patients who have been vaccinated against COVID-19 appear able to fend off all variants of SARS-CoV-2 in circulation, as well as ones that may soon emerge, a new study suggests. Their formidable antibodies may even protect against coronaviruses in other species that have yet to make the jump into humans—and may hold clues to how to make a so-called pancoronavirus vaccine that could forestall future outbreaks.

A team led by emerging disease specialist Linfa Wang from Duke-NUS Medical School in Singapore identified eight SARS survivors who recently received two shots of a messenger RNA COVID-19 vaccine. In the test tube, antibodies sieved from their blood potently “neutralized” an early strain of SARS-CoV-2 as well as SARS-CoV, the virus that caused SARS, Wang and colleagues report today in The New England Journal of Medicine. The team further found these neutralizing antibodies worked well against the Alpha, Beta, and Delta variants of SARS-CoV-2 and stymied five related coronaviruses found in bats and pangolins that potentially could infect humans.

This study’s demonstration of broad spectrum immunity against sarbecoviruses—a subset of coronaviruses that includes the causes of SARS and COVID-19—is “amazing and very good news,” says Priyamvada Acharya, a structural biologist at Duke University who works on pancoronavirus vaccine research and was not involved in the new study. “This paper provides a proof of principle that a pansarbecovirus vaccine is possible.” It also marks an important step toward a long-term hope—a vaccine that works against all coronaviruses—several researchers trying to develop this dreamed of protection say.


SARS-CoV and SARS-CoV-2 are about 80% identical, and both initiate infections when their surface protein, spike, binds to the human cellular receptor known as angiotensin-converting enzyme 2 (ACE2). So Wang was surprised this year when other researchers reported that people who had recovered from SARS retained antibodies that could prevent SARS-CoV from binding to the ACE2 receptor, but didn’t seem to have any power against SARS-CoV-2. “It was always in the back of my mind that the two viruses bind to the same receptor, so why don’t [these people’s antibodies] cross neutralize?” he wondered.

The immune system’s B cells make a potpourri of antibodies against any virus, but lab tests typically measure the presence of the most abundant ones. Maybe SARS survivors harbored a population of B cells that recognized both SARS-CoV and SARS-CoV-2 but were in the minority and difficult to see, Wang reasoned. If so, he thought, a COVID-19 vaccine might bolster the population of those double-action B cells—and broaden survivors’ immunity.

To test that possibility, Wang’s team compared neutralizing antibodies from the vaccinated SARS survivors—all health care workers in Singapore—with those from SARS patients who had not received a COVID-19 vaccine. Wang’s team also analyzed antibodies in three other groups: unvaccinated people who currently had COVID-19, along with vaccinated people who had recovered from SARS-CoV-2 or had never been infected with that virus.

The vaccinated SARS survivors were the only cohort whose antibodies neutralized 10 different coronaviruses, according to a new assay Wang’s team developed that tests the antibodies’ ability to block binding between ACE2 and the receptor-binding domains (RBDs) of different spikes. And the levels of the neutralizing antibodies were relatively high against each one. “It’s superinteresting,” says Neil King, a biomedical engineer at the University of Washington, Seattle, who is also working on pancoronavirus vaccines. “It may lead people to reprioritize their efforts.”

Several groups working on pancoronavirus vaccines are combining spikes or just the key RBDs from eight or more different viruses. But the new work suggests a combination of just two may be enough to reach a less ambitious goal, protecting against all sarbecoviruses. Then again, Wang has yet to identify why these antibodies work so well, which is critical to designing vaccines because the RBDs themselves likely will not trigger production of the wanted immune response. The design of what are known as immunogens will require a complicated structural biology analysis, now underway in his group, that can determine precisely where they bind to the RBDs. That information, in turn, might allow researchers to reverse engineer the parts of spike that trigger production of these antibodies.

For a booster shot against possible SARS-CoV-2 variants or a pansarbecovirus vaccine, Wang suggests the best immunogens would combine common regions of SARS-CoV and the SARS-related viruses from pangolins and bats. “We want the vaccine to be as far away as possible from SARS-CoV-2, so that you really get the human immune system to work out only the common neutralizing antibody,” he says.

In parallel with the vaccine work, the lab has also isolated several individual antibodies from the COVID-19–vaccinated SARS survivors that are “much more potent” against SARS-CoV-2 than anything described by other groups. Made in quantity in the lab, those monoclonal antibodies could play a critical role in future outbreaks, Wang thinks. “We are going to produce a cocktail of a dozen monoclonal antibodies that neutralize all the different sarbecoviruses and are ready to fight the next pandemic,” he says. “If we are unfortunate enough to have a SARS-3 down the line, we’ll already have a therapeutic cocktail ready to go.”

Andrew Ward, a structural biologist at Scripps Research who is developing pancoronavirus vaccines, calls the results from Wang’s team “pretty cool,” although he isn’t surprised that immunity to both SARS-CoV and SARS-CoV-2 may generate a broader sarbecovirus shield. He is just as impressed that the study could even be done. Blood from the few SARS survivors is “a unique resource that that is hard to come by,” he says.

The combination of access to the SARS survivors in Singapore, which had the fifth highest number of cases of any country, and the new assay made this study possible, according to Wang. “No other lab could do this right now,” he says.