Human Antibody Responses to Infection and Vaccination
Laura M. Walker, Head of Infectious Disease Biotherapeutics Discovery & Engineering at Moderna
Antibody response data can inform vax design and aid fight against variants
A deeper understanding of how antibody-producing B cells respond to vaccines could help us better respond to variants of viruses like SARS-CoV-2 and plan immunization strategies.
The idea was outlined by Laura Walker, Ph.D., head of infectious disease biotherapeutics discovery and engineering at Moderna, who shared details of studies looking at B cell response to vaccines against several diseases, including yellow fever, Zika and COVID-19 at the Antibodies Engineering and Therapeutics US 2023 conference in San Diego, Calif.
And, while the studies examined very different viruses and vaccine technologies, including Moderna’s own mRNA-based SARS-CoV-2 jab, there were similarities in B cell response that should inform vaccine development, according to Walker.
“There are a few practical implications for vaccine design that I thought might be worth highlighting. So one is something that we all kind of already know but it’s been sort of discovered empirically, which is that the long interval that we normally have between a prime and a boost improves antibody responses,” she said.
“And this sort of gives you the mechanistic explanation for it, which is that memory B cells are evolving over that six months, and then when you do the boost, you’re boosting an affinity-matured population.”
This finding has public health implications, according to Walker, who cited immunization plans as an area that could be applied.
“For a seasonal COVID booster, this provides some rationale potentially due to two doses followed by a few months to allow maturation of those memory B cells. And then the boost would expand that memory B cell compartment,” she said.
Escape mutants
The knowledge that spacing out B cell priming and the application of a booster also better positions us to deal with so-called “escape mutants” — genetically distinct viral variants to which the antibodies in immunized people do not bind.
“We also think that there might be some value in sort of monitoring neutralizing antibody responses to infection and vaccination to try to provide some insight into future viral evolution because there’s these types of antibodies that are really pressuring the virus,” Walker said.
“So their escape mutations often give you sort of a roadmap to what’s coming next, or at least that’s what we’ve seen in the context of SARS-CoV-2. And that might sort of inform on the need for boosters or strain updates, [and] maybe you could get ahead of the virus this way.”
Vaccine design
According to Walker, understanding how antibody production evolves could also guide the development of new jabs, as exemplified by the design of epitopes — the part of the vaccine that elicits B cell response.
“… I think if we could come up with strategies to really broaden epitope coverage, that would help us to reduce the public nature of the response at the population level and limit that immune pressure,” she said.
Walker said that the potential benefits of this approach could be significant, particularly during future pandemics or even seasonal disease outbreaks.
“You might be able to limit viral evolution as well and sort of slow the virus down. And that I think is something to think about in the context of COVID-19 and also influenza.”
