CoronaVac: Does it work against the Gamma variant?

The CoronaVac vaccine shows significantly reduced neutralizing activity against the Gamma variant (previously known as P.1) of SARS-CoV-2 — indicating that the variant may be able to escape immune response in fully vaccinated people as well as reinfect those who had recovered from COVID-19, according to an immunological study presented at ECCMID 2021.

“Neutralizing antibodies are an important component of the immune response against SARS-CoV-2.  Therefore, the capacity of the P.1 variant to evade antibodies present in the plasma of CoronaVac-immunized individuals suggests that the virus can potentially circulate in vaccinated individuals —  even in areas with high vaccination rates,” said principal investigator Dr Jose Luiz Proença-Módena from the University of Campinas, Campinas, Brazil.

The P.1 variant was first discovered in Brazil and harbours 15 unique mutations, including three key mutations at Lys417Thr, Glu484Lys, and Asn501Tyr in the S-protein receptor-binding domain that are also present in the Beta lineage.

To compare the neutralizing activities of antibodies on lineage P.1 vs lineage B of SARS-CoV-2, the researchers collected plasma samples from 53 recipients of the CoronaVac vaccine and 21 individuals who previously had COVID-19. The 53 vaccinated individuals comprised 18 people who had received a single dose (20-23 days earlier) and 20 fully vaccinated individuals with complete two doses (second dose 17-38 days earlier) during the Brazilian vaccination programme, plus 15 individuals who had been fully vaccinated in a phase III randomized trial (collected 134-230 days after second dose). [Lancet Microbe 2021;doi:10.1016/S2666-5247(21)00129-4]

Among previously infected individuals, the plasma neutralization activity against P.1 were 8.6 times lower compared with that against the lineage B isolate (VNT₅₀*, 30 vs 260) — which translates to a significant reduction against lineage P.1 (p≤0.0001) based on a binomial modelling.

There was no efficient neutralisation** of P.1 isolate detectable, regardless of whether it was using samples from individuals with only a single dose of vaccination or who had been fully vaccinated.

Although there were some neutralization activities (VNT₅₀, 24-28) detected for samples collected from those who had recently completed two vaccine doses (second dose 17-38 days earlier) in the national immunization programme, the neutralizing antibody titres were still markedly reduced against lineage P.1 vs lineage B isolates (1:20 vs 1:80).

“The data suggest that P.1 lineage virus might escape from neutralizing antibodies induced by an inactivated SARS-CoV-2 vaccine, especially at 5 months after vaccination as immunity wanes,” said Proença-Módena and co-authors. “Our results also suggest that the P.1 variant can escape from neutralizing antibody responses generated by previous SARS-CoV-2 infection and thus reinfection might be possible.”

“[This] suggests that variants of concern might escape population immunity and continue to circulate in populations, even with high vaccination coverage with inactivated vaccines,” they pointed out.

Nonetheless, the authors also noted that CoronaVac can still protect against severe COVID-19 and death overall, based on results of a phase III trial. “Therefore, neutralizing antibodies might not be the only contributing factor — the T-cell response may also play an important role in reducing disease severity,” they explained.

“Consequently, continued and enhanced genetic surveillance of SARS-CoV-2 variants worldwide, paired with plasma neutralising antibody assays is required to guide updates of immunization programmes,” suggested the researchers.

*VNT₅₀: median virus neutralization titre

**VNT₅₀ below the limit of detection [<20]