What does the future Covid-19 vaccine look like? It has to be multivalent

Dr Agarwal is the Dean of Biosciences and Health Research at the Trivedi School of Biosciences of Ashoka University. He is a trained pulmonologist whose research focusses on respiratory disease biology. He was at the helm of the Institute of Genomics and Integrative Biology when the pandemic hit and has been a key expert in the government’s pandemic response. With IGIB being one of the ten hub laboratories under India’s Covid-19 genomic sequencing consortium, Dr Agarwal headed the team till his retirement earlier this year. He is also the Chair and only Indian member of the World Health Organisation’s Technical Advisory Group on Sars-CoV-2 Virus Evolution.

The national drug regulator has approved India’s first Covid-19 vaccine that can be given as a nasal drop for emergency use in adults. Although a primary vaccine – to be given as the first and second dose against Covid-19 – and most adults who have received other vaccines would not be eligible for it, experts say that it is an important development in vaccine technology that’s likely to prevent transmission of the disease. Dr Anurag Agarwal, Dean of Biosciences and Health Research at the Trivedi School of Biosciences of Ashoka University, talks about how the next generation vaccines could look like.

There is a growing vaccine hesitancy among people, especially for the third dose, now that the rates of infection and hospitalisation associated with Covid19 are low. Could the introduction of the nasal vaccine change that?
If we talk about breakthrough infections (infections despite vaccination), they are likely to continue unless we have a vaccine that has a high protection against the variants in circulation. However, we know that even with the existing vaccines, the likelihood of severe disease and hospitalisation goes down. So, it is important that the elderly and those with co-morbidities – who are at the highest risk of getting severe disease – take their third shot. Children, in whom the infection is anyway mild, would not need it so much. And, that is what our vaccination drive also focuses on.

When it comes to which vaccine to take as a booster dose, the protein-based ones (BiologicalE’s Corbevax is one such vaccine that has been approved as a mix-and-match booster by the government) would be the best. And, now we also have the nasal vaccines.

Would the nasal vaccine help in cutting the transmission of the infection?

We do not have any data to say that for sure. However, since the nasal vaccine gives you local immunity (in the nose where the virus first enters) we can say that it is more likely to be effective at preventing transmission than the current generation of vaccines we have. But there is still room for improvement. This is one step in the multitude of next generation of vaccines.

What should we look for in the next generation of Covid-19 vaccines?

The next generation of vaccines should have three things. First, something like the nasal vaccine works. That’s because it provides local immunity as well as convenience of administering with no need for syringes and trained manpower. Second, it should be practical and affordable. This would mean not only lower costs but also easy distribution, no need for cold chains with very low temperatures and so on. Third, it should be multivalent so as to cover a wider spectrum of Sars-CoV-2 virus.

When we talk about multivalent vaccines, which variants should be considered? And how are these different from pan-sarbecovirus vaccines that are also being explored by some?

When we talk about multivalent vaccines, it will be against several variants of Sars-CoV-2 but we have to start with bivalent vaccines first. Since the ancestral variant is already in use in most of the Covid-19 vaccines, companies would likely retain that. In addition, one of the Omicron variants such as BA.1, BA.2, BA.4, or BA.5 may be used. A vaccine like that will provide a nice protection against most variants, including the Delta. A combination of ancestral and BA.1 (which was one of the variants that caused the January surge) will provide the widest protection while a combination with BA.4 or BA.5 will provide good protection against the variants in circulation. If we plan to add more than one variant, Delta might also be added.

But, why stop at just that, more things can be imagined for the next generation of vaccines. When we talk about Sars-CoV-2, the spike is not the only antigen (the part of the virus that elicits an immune response), there are multiple possible antigens across the virus. And pan-sarbecovirus vaccines (vaccines that protect against Covid-19 along with other viruses from the same family such as the one that causes SARS) depend on this principle.

Studies show that there are antigens that are preserved across all sarbecoviruses. It was seen that people who recovered from SARS (which caused an outbreak in 2003) and got a Pfizer original variant vaccine, were not only able to fight off Sars-CoV-2 well but other sarbecoviruses. So, in theory, certain combinations of Sars-CoV-1 and Sars-CoV-2 can protect against the entire family.

Other than that, there are now also several interesting papers that are coming out on vaccine technology. My bet is on self-assembling protein nanoparticles. So, there are certain molecules, such as the protein ferratin (a blood protein that contains iron) that are made up of multiple units that assemble themselves in a particular pattern. Now, imagine each of these units is tagged with different antigens, say different variants of Sars-CoV-2, and then thrown together. They will come together to become a nano-particle with different antigens that can be given through the nose to protect against several variants.

Of course, these platforms can be used not only for Sars-CoV-2 but a host of other infectious diseases as well.

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