mRNA Vaccine Booster Shots Likely Required Within Six Months To Protect Against Covid-19 Variants

(Posted on Tuesday, May 11, 2021)

The majority of new infections in the US, Europe, and most other countries are now driven by variants. Until recently, the B.1.1.7 variant was the most dominant strain in the UK and throughout Europe and is prevalent in the United States as well. In South Africa the dominant strain is the B.1.351 variant; in South America, the P.1 variant. Now in India, three closely related strains, B.1.617.1, B.1.617.2, and B.1.617.3, are now running rampant. The B.1.617.2 variant has appeared in the UK as well. These variants of SARS-CoV-2 are highly transmissible, capable of reinfection, and cause more serious disease. They also introduce the distressing possibility that current generations of Covid-19 vaccines may not protect as well against these variants as they do original strains.

A new preprint study conducted by Moderna describes both the hope and challenge of booster vaccines as an approach to the solution to the problem of variants. Their booster shots appear to be effective at neutralizing at least two of the new variants, B.1.351 and P.1. But importantly, their preprint study also revealed the first-generation Moderna vaccine doesn’t protect against the variants for as long as we initially hoped.

The phase II study compared the efficacy of two different additions to the existing two-dose regimen: half a dose more of the vaccine developed based on the original strain, or a full dose of a new vaccine based on the B.1.351 variant first detected in South Africa. (A version that combines the two is also in the works, though the data has yet to be released.) Using lab-grown virus, the researchers found that both approaches raised neutralizing antibody levels to impressive new heights (see Figure 1C). No indication was given as to when these boosters might be available to the general public, but it is probably safe to assume these will be fast-tracked for approval.

The commendable performance of the booster shots wasn’t the only finding to emerge from the study, however. The researchers also confirmed what we’ve long suspected based on laboratory studies. When tested for its ability to neutralize the P.1 and B.1.351 strains, the antibodies generated by the Moderna vaccine against the original strain dropped to low or undetectable levels six to eight months after the second dose (see Figure 2).

For months we have speculated as to how long immune protection from the first-generation vaccines would last against the original strain and new variants. Thanks to this new study, the answer is becoming clearer for the Moderna vaccine, which together are considered substantially more potent than other vaccines. I’ve called the mRNA vaccines created by Moderna and Pfizer the Lamborghini of vaccines for a reason. If two doses of the Moderna vaccine amount to six months of protection against the variants, other vaccines are likely to guarantee less.

No surprise is it that the protection afforded by vaccination is less against the variants. The only factor we didn’t adequately consider was timing. Studies published in the spring and summer of 2020 indicated that neutralizing antibodies induced by natural infection were quick to fade. We can now predict that this is the case for vaccine-mediated antibodies too.

This doesn’t necessarily imply a direct loss of immune protection. When antibodies fade, the combined defenses of T cells, memory B cells, and other components of the immune response may suffice. But given that neutralizing antibodies have been our most reliable measure of immunization thus far, it would be irresponsible and shortsighted to disregard the correlation and hope for the best. Optimism is a salve in times of crisis, but it can’t prevent or cure mass infection.

In most countries, new SARS-CoV-2 variants have superseded the original strain as the predominant form of the virus. The highly infectious B.1.617 variant is thought to be one of the main drivers of the Covid-19 surge in India, where the number of new cases recorded in a single day toppled 400,000 multiple times in past weeks. B.1.617 is now wreaking havoc on India’s smaller next-door neighbor, Nepal; in just two weeks cases have shot up almost 700 percent. The same variant has recently been detected in the Philippines, France, Singapore, and the UK. On Monday England’s chief medical officer warned the prevalence of B.1.617 had “gone up sharply”—a sign of foreboding in a country where the B.1.1.7 variant overwhelmed health systems earlier this year.

Notably, the B.1.617 variant wasn’t included in the new Moderna study. Compared to the B.1.351 and P.1 variants that were, B.1.617 is both more evolved and more dangerous. Whether it requires a homologous booster of its own remains to be seen. For now, we can at least take comfort in the fact that variant-proof booster shots are attainable, effective, and on their way.

To anyone who has already been fully immunized with the mRNA vaccines, either from Moderna or Pfizer, I recommend you note in your calendar when you received your second shot. Six months from then, it might be time for your booster. If you’ve had any other vaccine, the time window is likely shorter. At present we can’t say with certainty how much shorter. The safest bet, given our current understanding of vaccines and variants, is to plan for relatively frequent boosters for some time to come.

Originally published on Forbes (May 11, 2021)