South African Variant Escapes Sputnik Vaccine
A study on COVID variants using in vitro tests, available on the preprint server medRXiv, has shown that the South African variant escapes the Sputnik V vaccine.
This study is the first of its kind to show Sputnik V vaccine recipients had reduced neutralising capacity against the B.1.351 and E484K mutant spikes.
When it comes to vaccine design, the most effective vaccines use a stabilised form of the spike protein, while others use the wildtype spike, protecting against severe disease but not infection because of lower levels of neutralising antibodies. A number of SARS-CoV-2 variants of concern (VOC) have mutations on the spike protein, or the E484K mutation, which allows it to escape vaccines and prior immunity.
In South Africa, where 93% of infections are due to B.1.351, the AstraZeneca vaccine, based on the wild-type spike, failed to prevent mild-to-moderate COVID. The Sputnik V or Gam-COVID-Vac vaccine is also based on the wild-type spike. Interim Phase 3 trial results reported an efficacy of 92%, but this excludes current variants and any lineage containing E484K.
The current study examined serum neutralisation activity in samples obtained from 12 recipients of the Sputnik V vaccine in Argentina. This country has already detected many independent variants with E484K, with or without N501Y substitutions.
The researchers found that pseudoviruses bearing either the wildtype D614G spike, and the B.1.1.1.7 spike were effectively neutralised by the vaccine sera, in live virus plaque reduction neutralisation assays. The geometric mean titer of neutralising titers was 49, similar to that of the phase III trial.
However, these sera showed moderate to a marked reduction in neutralisation titers against spike protein bearing E484K, and the UK variant. Even at the highest serum concentration used, 9 of the 12 serum samples could not inhibit 50% of B.1351 viral particles, and only half the sera did so against the E484K mutant.
The researchers concluded that, relative to the wildtype spike virus neutralising titers, were reduced by seven-fold against the B.1.351 lineage and three-fold against the E484K spike. They also found that the VOCs with the different spikes showed different modes of escape from antibody-mediated neutralisation by sera elicited by the Sputnik V vaccine. This means that resistance to neutralisation offered by the South African variant occurs by a different mechanism than that of the E484K mutant.
The UK VOC has low resistance to pre-existing or vaccine-induced antibodies, but the B.1.351 variant shows marked resistance. In fact, 8 of 12 samples were unable to reach IC90 at the highest possible serum concentration.
One neutralised the UK variant but none of the other three variants. These findings are of particular concern because all three VOCs carry the N501Y RBD substitution that confers increased affinity for the ACE2 receptor.
This resistance is competitive and is not present at higher serum concentrations. However, this is not true for the mutations in the B.1.351 variant, which escapes neutralisation with undiluted serum.
Though the Sputnik V vaccine likely protects against severe COVID from VOCs, it is troubling that B1.351, as well as all E484K-bearing mutants, is resistant to neutralisation by sera elicited by this vaccine.
However, antibody functions may be different in vivo, and this study does not cover cell-mediated immunity to multiple antigen sites.
“Taken together, our data argue that surveillance of the neutralizing activity elicited by vaccine sera will be necessary on an ongoing basis,” the authors wrote.
The knowledge of which variants can still spread among vaccinated and naturally immune individuals will help decide how to contain them with vaccine upgrades.
Source: News-Medical.Net
Preprint information: Ikegame, S. et al. (2021). Qualitatively distinct modes of Sputnik V vaccine-neutralization escape by SARS-CoV-2 Spike variants. medRxiv preprint. doi: https://doi.org/10.1101/2021.03.31.21254660. https://www.medrxiv.org/content/10.1101/2021.03.31.21254660v2
