Opinion: “How to Redesign Covid-19 Vaccines So They Protect Against Variants”
Given that the SARS-CoV-2 variants can evidently evade immunity produced by vaccines or previous infections, scientists are exploring the idea of redesigning the vaccines currently being rolled out worldwide. While researchers are still debating whether the new variants have an effect on the first generation Covid-19 vaccines, some vaccine developers are charging forward with plans to update their shots so that they more effectively target emerging variants. These lineages carry mutations that seem to dampen the effects of antibodies crucial to fending off infection. Researchers are considering following the strategy used by influenza vaccines, meaning that they would update Covid-19 vaccines periodically and readminister them to the public.
According to Mani Foroohar, a biotechnology analyst at the investment bank SVB Leerink in Boston, the best strategy to combat the threat of emerging variants is to “vaccinate as many people as possible with current shots”. This is only a strategy to use until the future vaccines become effective against these variants.
Will we need updated Covid-19 vaccines?
According to some virologists, updating Covid-19 vaccines will be necessary. Labs are working around the clock to understand how effective the vaccines are against the new variants. Up until recently, the million-dollar question, according to Kanta Subbarao, a virologist at the Peter Doherty Institute for Infection and Immunity, is whether these changes are enough to lower the effectiveness of the vaccines, because we don’t know how much antibody is required.
As of the 28th of January, Biotech firm Novavax released data from clinical trials which showed their experimental vaccine being around 60% effective against the 501Y.V2 (South African) variant. Two COVID-19 vaccines from Chinese companies including Sinopharm also had weaker effects when it triggered immunity against a highly transmissible coronavirus B.1.1.7 variant, shown in this study conducted.
“I think it’s inevitable for the vaccines to maintain tip-top efficacy, they will need to be updated. The only question is how often and when,” says Paul Bieniasz, a virologist at the Rockefeller University in New York City who co-led one of the neutralizing-antibody studies.
How should we decide when to update vaccines?
Scientists are only now learning how different mutations are altering vaccine response. By following models of other vaccines, it can create a potential blueprint in our fight against Covid-19. According to Subbarao, “One model that COVID vaccine updates could follow is that of seasonal flu vaccines”. Subbarao also directs the World Health Organization Collaborating Centre for Reference and Research on Influenza in Melbourne. One of her objectives is to monitor emerging flu changes that may have influential characteristics on the vaccines’ effectiveness but to act upon changes “ only when a vaccine-evading strain is widespread”. This comes from the fact that it would not be viable to change a vaccine if the vaccine-evading strain is concentrated to a region or a country. “We can’t be chasing every variant that emerges,” says Subbarao.
How will the vaccines be updated?
There are three potential approaches that are being considered. Given that fact that the variants including 501Y.V2 carry spike mutations that alter regions targeted by neutralizing antibodies. So, one approach is to just swap the vaccines’ old versions of the spike protein with an updated version that has the specific amino-acid changes that hinder antibody responses. As simple as it sounds, researchers are still to determine if any changes may lead to other effects which may alter the immune response to the vaccine.
A second approach is to look at a multivalent vaccine, which includes both new and old forms of spike protein. Just like the first approach, “It’s not going to be as simple as [altering] an amino acid site and saying, ‘okay we got it’”, says Subbarao. Studies will need to be conducted on animals and humans before any update is made to the vaccines.
The third and final approach could be using T-cells (‘Killer Cells’). Being a group of immune cells that can target and destroy virus-infected cells, T-cells have the potential of replacing antibodies in regards to long term immunity. “It makes sense biologically. We don’t have the data, but we can hope” says Daina Graybosch, a biotechnology analyst at investment bank SVB Leerink in New York City.
According to Annika Karlsson, an immunologist at the Karolinska Institute in Stockholm, T cells can help mitigate the severity of the infection. “T-cells could mean the difference between a mild infection and a severe one that requires hospital treatment,” she says. Since antibodies only detect proteins that are outside the cell, this approach is different than the first two as the T-cells can target viral proteins expressed inside infected cells, and some of those proteins are very stable, she says. Given that many viruses target the spike protein (found on the surface of the cell), it may succumb to mutation and may increase the risk of emerging variants as spike protein tend to be variable. Researchers have discovered similarities and differences between the features of all beta coronaviruses that cause human disease, which allude to the idea that T-Cells may be the way to go.
Approvals and trials for the new vaccine
With the first-generation vaccines already being distributed worldwide, testing updated vaccines is going to be slow and difficult. Looking at the seasonal flu vaccines, they do not tend to require fresh trials. But we must keep in mind that in contrast to the seasonal flu, we do not have the substantial clinical data (from years of experience) Covid-19 to follow the same suit.
By focusing on markers such as ‘correlates of protection’ (measurable features of an immune response), researchers can reduce the timeline in our benefit. By measuring the immune response after each doses, researchers will save on time as they will not have to wait for the trial participants to be infected with the coronavirus to know if the vaccine is effective or not.
William Haseltine is president of ACCESS Health International. An infectious disease expert, Haseltine was formerly a Harvard Medical School professor and founder of the university’s cancer and HIV/AIDS research departments. His latest book is titled Variants! The Shape-Shifting Challenge of Covid-19.