As public health authorities and governments struggle to turn to the tide of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (COVID-19), newly emerged and highly infectious variants place increased stress on containment measures.
Newly approved vaccines are being distributed to millions the world over, but concern is mounting over whether they will elicit antibodies capable of neutralizing the new variants with their array of mutations.
A new preprint released on the bioRxiv* preprint server offers some reassuring findings, reporting the successful neutralization of the South African SARS-CoV-2 variant of concern (VOC) 501Y.V2 by two vaccines developed in China.
New variants emerge
Soon after the declaration of the COVID-19 pandemic, the D614G mutation emerged, and the strain carrying it rapidly became the most common variant worldwide. Recently, a variant of concern has emerged in the UK, the so-called ‘501Y.V1’ variant, which has a much stronger binding affinity and is markedly more transmissible than earlier variants.
Soon afterwards, the isolation of the 501Y.V2 strain from South Africa, and a third from Brazil, signified the emergence of potentially dangerous new variants from all over the world. Early studies indicate that the 501Y.V2 may be more virulent and more transmissible, making its control and treatment an urgent necessity.
The two vaccines the research team assessed are the licensed inactivated vaccine BBIBP-CorV and the recombinant dimeric receptor-binding domain (RBD) vaccine ZF2001. Both elicit antibodies targeting the viral spike antigen, which mediates viral entry into the host cell.
Though one targets the whole virus, and the other the RBD in dimeric form, both of these vaccines are known to be highly immunogenic. In its clinical trials, ZF2001, for example, was shown to elicit neutralizing antibodies at geometric mean titers (GMTs) two-fold that of convalescent plasma.
The South African variant
The 501Y.V2 variant has 10 amino acid changes in the viral spike receptor-binding domain (RBD). It has now been isolated from several countries after its initial discovery in a South African pilot.
Of the ten mutations in the spike protein, five are in the N-terminal domain (NTD), three in the RBD, and two in the C-terminal domain and the S1/S2-S2’ region.
These mutations have been found to allow viral escape from neutralization by convalescent plasma from COVID-19 patients, as well as from sera from vaccinated individuals who had received mRNA vaccines.
In addition, a phase 3 clinical trial of a protein-based vaccine constructed around the trimeric spike protein showed that the induced antibodies were much less effective at protecting against infection with the new variant.
These results have evoked enormous concern, as the ongoing rollout of vaccines envisages the induction of population immunity worldwide, to halt the pandemic. If the vaccines now being used cannot induce effective immunity, the vaccination efforts will be largely useless as the new variants are rapidly becoming dominant.
Intact neutralization efficacy
The current study tested the neutralizing efficacy of sera taken from 12 clinical trial participants, with the serum neutralizing activity covering a range of titers. The researchers used a microcytopathogenic effect assay to reflect the presence of infectious virus; that is, non-neutralized virus, after exposure to the antisera.
In all 12 samples, the sera showed that the two vaccines evaluated retained their neutralizing efficacy against the 501Y.V2 variant, almost unchanged when tested against the ancestral Wuhan strain or the globally dominant D614G strain
The only change was that the GMTs fell by 1.6 times, compared to those achieved against the Wuhan or D614G variants. With BBIBP-CorV, the GMT declined from 110 to 71, and for ZF2001, from 106 to 67%.
When compared with the decline in GMT by tenfold with convalescent plasma, and six-fold with sera from individuals vaccinated with mRNA vaccines, this 1.6-fold decline is significantly smaller. However, this should be compensated for when describing the clinical efficacy of these vaccines.
The neutralizing efficacy of these vaccines is unaltered, despite the fall in GMTs. “These data indicated that 501Y.V2 variant will not escape the immunity induced by vaccines targeting whole virus or RBD,” say the researchers.
The researchers plan further work to understand the difference in GMTs against the background of intact neutralizing ability.
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.