Sputnik Vaccine Ineffective Against the South African Variant

Most vaccines now in use or being developed focus on generating antibodies to the viral spike protein, which mediates host cell entry and infection. This is based on the strong correlation between neutralizing antibodies to the spike and protective immunity.

The vaccines with the highest efficacy use a stabilized form of the spike protein with two paired proline substitutions, locking it into the prefusion form. Others, which use the wildtype spike, may protect against severe disease but not against infection because of the lower levels of neutralizing antibodies. This has been observed to be true of the Astra-Zeneca ChAdOx1 vaccine, based on an adenovirus vector.

In South Africa, where 93% of infections are due to B.1.351, the vaccine failed to prevent mild-to-moderate COVID-19. The Sputnik V or Gam-COVID-Vac vaccine is also based on the wild-type spike. Its interim Phase 3 trial results have been reported to show a vaccine efficacy of 92%, but this did not include the currently circulating variants nor any lineage containing E484K. The current study assays serum neutralization activity in samples obtained from a dozen Sputnik V vaccine recipients in Argentina.

This country has already detected many independent E484K-bearing variants, with or without N501Y substitutions, in tandem with its vaccine rollout. The researchers found that pseudoviruses bearing either the wildtype D614G spike and the B.1.1.1.7 spike were effectively neutralized by the vaccine sera, in live virus plaque reduction neutralization assays.

The geometric mean titer (GMT) of neutralizing titers was 49, similar to that of the phase III trial. However, these sera showed moderate to a marked reduction in neutralization titers against spike protein bearing E484K, and the UK variant. Even at the highest serum concentration used, 9/12 serum samples were not capable of inhibiting 50% of B.1351 viral particles, and only half the sera did so against the E484K mutant. The researchers concluded that virus neutralizing titers (VNTs) were reduced by seven- and three-fold against the B.1.351 lineage and E484K spike, respectively, relative to the wildtype spike. When the vaccine was tested by assaying the inhibition of the wildtype and VOC spike proteins using soluble RBD-Fc, the spike-receptor affinity was found to follow classical dose-response curves. The Fc component of an antibody is the part that recognizes the receptor, in this case, the human angiotensin-converting enzyme 2 (ACE2). Both the UK and the South African variant showed a slight decrease in RBD-Fc inhibition of viral entry, with a 1.5- and 2-fold rise in the IC50, respectively. This might have been expected from the fact that they both have the N501Y substitution associated with enhanced RBD-ACE2 affinity. However, this is not consistent with the sensitivity of the UK variant spike in virus neutralization assays, as shown earlier. Thus, the findings suggest that the VOCs with these different spikes show different modes of escape from antibody-mediated neutralization by sera elicited by the Sputnik V vaccine.

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Ref Link: https://doi.org/10.1101/2021.03.31.21254660.

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