Researchers in the United States have demonstrated the efficacy of Moderna’s coronavirus disease 2019 (COVID-19) vaccine at protecting against the South African B.1.351 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in non-human primates.
The non-human primate model has previously been crucial for guiding the development of vaccines that protect against COVID-19 in humans.
Robert Seder from the National Institutes of Health in Bethesda, Maryland, and colleagues report that two doses of Moderna’s mRNA-1273 vaccine significantly reduced viral replication in the upper and lower airways and limited inflammation in the lung, after the animals were challenged with the B.1.351 variant.
However, the vaccine dose and number of immunizations had a significant effect on the protective capacity observed.
Animals that were immunized with a single 30µg dose showed no detectable neutralization activity against B.1.351, whereas two 100µg doses generated effective immunity and quickly controlled viral replication in the upper and lower airways.
“These data highlight the importance of a prime and boost regimen for optimizing neutralization antibody responses, particularly against B.1.351 and likely for any other variant of concern for which vaccine-induced neutralization is decreased,” writes the team.
A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.
The concerns surrounding emerging variants
The Moderna mRNA-1273 vaccine is a messenger RNA-based vaccine that encodes the full-length spike protein of the original Wuhan-Hu-1 strain of SARS-CoV-2. The spike protein is the main structure the virus uses to bind to and infect host cells and the primary target of neutralizing antibodies following infection or vaccination.
Vaccination with two 100µg doses of mRNA-1273 was shown to be 94% effective at protecting against symptomatic COVID-19 when the Wuhan-Hu-1 and D614G variants were the dominant circulating strains.
However, the emergence of SARS-CoV-2 variants that exhibit resistance to neutralization by sera from Wuhan-1 strain convalescent subjects or vaccinees has led to concerns about the effectiveness of vaccines against the variants.
To date, the most concerning variants contain mutations in the spike protein’s receptor-binding domain (RBD) that are associated with increased transmissibility and resistance to neutralizing antibodies.
The B.1.351 variant is particularly worrying
Among these variants, which initially emerged in the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1 ), New 73 York (B.1.526), and California (B.1.427/B.1.429), the B.1.351 lineage contains the most concerning set of mutations.
“We and others recently reported that sera from mRNA-1273-immunized human and non-human primates (NHPs) showed the greatest reduction of neutralization against B.1.351 compared to the B.1.1.7, P.1, and B.1.427/B.1.429 variants,” says the team.
Furthermore, human efficacy trials of the mRNA-1273 vaccine have not yet been conducted in regions where B.1.351 is the dominant circulating variant.
What did the researchers do?
The design and development of COVID-19 vaccines has previously benefitted from clinically translatable results generated in studies of NHPs. The researchers, therefore, evaluated the impact of the mRNA-1273 vaccine on immunogenicity and protection against challenge with B.1.351 and D614G in this animal model.
NHPs were administered 30 or 100µg of the vaccine as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30µg at week 0, or no vaccine (control group).
What did the study find?
The team found there was a dose-dependent increase in Wuhan-1 and B.1.351 spike- and RBD-specific antibody titers and D614G and B.1.351 neutralization titers.
Importantly, while there were detectable levels of neutralizing antibodies against D614G following a single 30µg dose of the vaccine, there were no detectable neutralizing antibodies against B.1.351.
By contrast, eight weeks after NHPs had received a second 100µg dose of the vaccine, neutralizing antibody titers against both D614G and B.1.351 were detected.
Two days following challenge with B.1.351 challenge, viral single guide RNA (sgRNA) in bronchoalveolar lavages (BAL) was undetectable in six of eight NHPs that received two 100µg doses, and there was an approximate 2-log reduction in sgRNA among NHPs that received two 30µg doses, compared with controls.
In nasal swabs, a 1-log10 reduction in viral sgRNA was observed among the animals that received two 100µg doses and there were limited levels of inflammation and viral antigen in the lungs.
“Immunization with two doses of mRNA-1273 achieves effective immunity”
“Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHPs,” says the team.
The researchers say the durability of the immune responses is likely related to the maintenance of serum antibodies and memory B cells that can rapidly respond to a new viral antigen.
“Ongoing studies are assessing how additional boosting with spike antigens based on Wuhan-1 or variant strains will influence immunity and protection against B.1351 and other emerging variants in this model and in humans,” says Seder and colleagues.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.