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Cross-Neutralising Antibodies Bring Hope for Broad Vaccine to Combat COVID-19 Variants and Future Coronavirus Outbreaks

Findings from a recent study can underpin a “dream” vaccine that tackles not only SARS-CoV-2 and its known variants of concerns, but also future variants and animal coronaviruses that may cause fatal infections in humans.

According to the latest study by scientists from Duke-NUS Medical School and National Centre for Infectious Diseases, survivors of the 2003 SARS infection, who have been vaccinated with the Pfizer-BioNTech mRNA vaccine, produced highly potent functional antibodies that can neutralise all known SARS-CoV-2 variants of concerns and other animal coronaviruses that can potentially cause human infection. Their findings report the first incidence of cross-neutralising reactivity in humans, bringing hopes of developing an effective and broad-spectrum vaccine against various coronaviruses.

In the coronavirus family, there is one sub-group called sarbecovirus that relies on the ACE2 molecule to enter human cells. Both SARS-CoV-1 and SARS-CoV-2 belong to this group alongside a number of other coronaviruses that circulate in animals like bats, pangolins, and civets. While the exact route of transmission remains elusive, it is known that these viruses can jump from animals to humans and potentially start pandemics like the one we are currently battling.

Considering the threat these viruses pose, Dr. Chee Wah Tan and his colleagues from Duke-NUS’s Emerging Infectious Diseases programme sought to investigate potential solutions and remedies. “We explored the possibility of inducing pan-sarbecovirus neutralising antibodies that can block the common human ACE2-virus interaction, which will be protective not only against all known and unknown SARS-CoV-2 [variants of concerns], but also future sarbecoviruses,” explained Dr Chee Wah Tan who is the co-first author of the study.

To test their hypothesis, the team recruited eight people who recovered from SARS-CoV-1, the virus responsible for the SARS epidemic in 2003. They also gathered ten healthy people and ten COVID-19 survivors. The researchers then compared the immune responses of the three groups before and after they were vaccinated with the SARS-CoV-2 vaccine. They hoped to determine whether the neutralising antibodies developed in the SARS-Vaccinated group could eliminate SARS-CoV-1, SARS-CoV-2, and other potentially zoonotic sarbecoviruses.

During the investigation, the scientists used an improved version of the surrogate virus neutralisation test to conduct their investigation. Developed by Professor Wang Linfa, who is the senior corresponding author of the study, the multiplex surrogate virus neutralisation test allows for the simultaneous detection of neutralising antibodies against different sarbecoviruses in a single tube, thus providing accurate side-by-side comparisons of neutralising antibody levels against different viruses.

According to Dr. Wanni Chia, the co-first author of this study, “Prior to vaccination, SARS-CoV-1 survivors had detectable neutralising antibodies against SARS-CoV-1 but no or low-level anti-SARS-CoV-2 neutralising antibodies. After receiving two doses of the mRNA vaccine, all displayed high levels of neutralising antibodies against both SARS-CoV-1 and SARS-CoV-2.” Furthermore, the Vaccinated-SARS-CoV-1 group was surprisingly the only group “with a broad spectrum of neutralising antibodies against ten sarbecoviruses that were chosen to be examined.”

With these findings, Professor Wang Linfa believes that their study can point to “a novel strategy for the development of next-generation vaccines, which will not only help [to] control the current COVID-19 pandemic, but may also prevent or reduce the risk of future pandemics caused by related viruses.” This is especially important “as emerging variants of concern have already demonstrated some degree of immune evasion against the first-generation vaccines,” as said by Associate Professor David Lye, Director, Infectious Disease Research and Training Office, NCID and joint corresponding author of the study.

Presently, the team is conducting a proof-of-concept study to develop a third-generation vaccine against different coronaviruses, soon to be called 3GCoVax. They are also working on broad neutralising antibodies for therapy and are looking to recruit individuals who recovered from the 2003 SARS infection as part of their ongoing studies. With further studies, it is hoped that their discoveries can help the world exit the pandemic. [APBN]

Source: Tan et al. (2021). Pan-Sarbecovirus Neutralizing Antibodies in BNT162b2-Immunized SARS-CoV-1 Survivors. New England Journal of Medicine.