- This study quantified neutralizing antibodies against pseudoviruses mimicking SARS-CoV-2 variants in 99 individuals who had received one or two doses of the Pfizer/BioNTech or Moderna COVID-19 vaccines
- Neutralization against many variants , such as B.1.1.7 (U.K.), was largely the same as with SARS-CoV-2 wild-type virus
- However, the P.2/P.1 (Brazilian/Japanese) and B.1.351 (South African) variants exhibited significant resistance even in fully vaccinated individuals, with decreases in neutralization antibodies of 3- to 7-fold and 19- to 42-fold, respectively
- Individuals who had received only a single recent vaccine dose had weaker neutralization titers overall, and most of them showed no neutralization at all against certain B.1.351 variants
- These results support the reformulation of existing vaccines to include diverse spike sequences; ultimately, development of new COVID-19 vaccines capable of eliciting broadly neutralizing antibodies may be necessary
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Both the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) vaccines against COVID-19 demonstrated >94% efficacy in phase 3 clinical trials conducted in multiple countries in late 2020. However, the emergence and wide circulation of multiple SARS-CoV-2 variants has raised concerns about the continued efficacy of these vaccines.
Research at Massachusetts General Hospital recently determined that the neutralizing antibodies induced by the vaccines are only partially effective against some of the variants. The results and their implications for vaccine development are discussed in Cell by Wilfredo F. Garcia-Beltran, MD, research fellow in the Mass General Department of Pathology; Alejandro Balazs, PhD, assistant professor at the Ragon Institute of Mass General, MIT and Harvard; and colleagues.
The researchers obtained blood samples from 99 adults, median age 33 (range, 22–73), who had received one or two doses of the Pfizer/BioNTech or Moderna vaccines. They used a high-throughput assay, developed at Mass General for HIV research, to assess neutralizing antibodies against pseudoviruses they designed to mimic SARS-CoV-2 variants.
The team focused on variants first described in the United Kingdom, Denmark, United States, Brazil/Japan and South Africa. The Brazilian/Japanese variants (dubbed P.1 and P.2) have been found in patients with documented SARS-CoV-2 reinfection. The South African variant (B.1.351) is also of great concern because multiple strains have emerged and because, like P.1, this variant bears three mutations in the receptor-binding domain of the spike protein, the main target of neutralizing antibodies.
Responses to Two Vaccine Doses
Among people who received two vaccine doses, most decreases in neutralization relative to wild-type SARS-CoV-2 were moderate (1.3- to 2.3-fold decreases).
However, decreases in the neutralization of the Brazilian/Japanese and South African variants were statistically significant (3- to 7-fold and 19- to 42-fold, respectively). In fact, 37% of Pfizer/BioNTech vaccine recipients and 43% of Moderna vaccine recipients showed no detectable neutralization of any of the three B.1.351 South African variants.
Responses to One Vaccine Dose
Individuals who had received only a single recent vaccine dose had weaker neutralization titers overall. None of them had detectable neutralization against two B.1.351 variants, except four individuals who reported previous COVID-19 infection or significant exposure, and one individual from whom no COVID-19 history was obtained.
Implications for Vaccination
Some countries, including Canada and the U.K., are making it their priority to give one dose of a COVID-19 vaccine to as many people as possible before providing second doses. In contradiction, this study emphasizes the importance of two-dose mRNA vaccine regimens to achieve sufficient titers, and perhaps breadth, of protection against novel SARS-CoV-2 variants.
The Pfizer/BioNTech and Moderna vaccines might provide benefit against P.1/P.2 and B.1.351 by reducing COVID-19 disease severity, but this has not been determined. Ultimately, it will be important to prevent transmission of SARS-CoV-2 variants, such as with vaccine boosters that specifically target diverse spike sequences or vaccines that elicit broadly neutralizing antibodies.
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