Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination

Abstract

Vaccines are proving to be highly effective in controlling hospitalisation and deaths associated with SARS-CoV-2 infection but the emergence of viral variants with novel antigenic profiles threatens to diminish their efficacy. Assessment of the ability of sera from vaccine recipients to neutralise SARS-CoV-2 variants will inform the success of strategies for minimising COVID19 cases and the design of effective antigenic formulations. Here, we examine the sensitivity of variants of concern (VOCs) representative of the B.1.617.1 and B.1.617.2 (first associated with infections in India) and B.1.351 (first associated with infection in South Africa) lineages of SARS-CoV-2 to neutralisation by sera from individuals vaccinated with the BNT162b2 (Pfizer/BioNTech) and ChAdOx1 (Oxford/AstraZeneca) vaccines. Across all vaccinated individuals, the spike glycoproteins from B.1.617.1 and B.1.617.2 conferred reductions in neutralisation of 4.31 and 5.11-fold respectively. The reduction seen with the B.1.617.2 lineage approached that conferred by the glycoprotein from B.1.351 (South African) variant (6.29-fold reduction) that is known to be associated with reduced vaccine efficacy. Neutralising antibody titres elicited by vaccination with two doses of BNT162b2 were significantly higher than those elicited by vaccination with two doses of ChAdOx1. Fold decreases in the magnitude of neutralisation titre following two doses of BNT162b2, conferred reductions in titre of 7.77, 11.30 and 9.56-fold respectively to B.1.617.1, B.1.617.2 and B.1.351 pseudoviruses, the reduction in neutralisation of the delta variant B.1.617.2 surpassing that of B.1.351. Fold changes in those vaccinated with two doses of ChAdOx1 were 0.69, 4.01 and 1.48 respectively. The accumulation of mutations in these VOCs, and others, demonstrate the quantifiable risk of antigenic drift and subsequent reduction in vaccine efficacy. Accordingly, booster vaccines based on updated variants are likely to be required over time to prevent productive infection. This study also suggests that two dose regimes of vaccine are required for maximal BNT162b2 and ChAdOx1-induced immunity.

Neutralization of SARS-CoV-2 Variants by rVSV-ΔG-Spike-Elicited Human Sera

“…Several months ago, the delta variant of concern (VOC) became dominant worldwide, exhibiting increased transmissibility, immune escape [9], and breakthrough infections in vaccinated individuals [10]. We therefore tested another set of 13 vaccinees' sera (Set 2, Table S2) for neutralization of the original virus and delta VOC.…”

“…As currently approved vaccines correspond to the original virus sequence [9,21], there is major concern regarding their ability to protect against SARS-CoV-2 variants. Neutralization titers against variants following two-dose vaccination with BNT162b2, mRNA-1273, or ChAdOx1 nCoV-19 were reported, showing for most only a minor reduction in alpha neutralization but a strong reduction in beta and gamma neutralization [13], while others reported no significant reduction in vaccine efficacy against the gamma variant [9,15,19]. An overall reduction in neutralization potential has been reported against the beta variant ranging between ~2-and 30-fold, depending on the report [15,17,19,22].…”

“…For the delta variant, some report a modest reduction in the effectiveness of two-dose vaccines compared to the alpha variant or to the original virus. Overall reduction ranges between ~2-and 11-fold [4,9,15,22].…”

Long-lasting cellular immunity to SARS-CoV-2 following infection or vaccination and implications for booster strategies

“…Notably, also in the case of natural infection, neutralizing antibodies decay slower than total anti-spike IgG and anti-RBD IgG. The progressive reduction of antibody levels may be the reason for the observed reinfections [24,25]. On the contrary, the frequencies of spike-specific B and CD4+ T cells are largely stable up to one year from hospital discharge.…”

The dynamic change of SARS-CoV-2 variants in Sierra Leone

“…The vast majority of these variants appear to be of little or no biological significance ( https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/ ). However, a small number of variants, termed variants of concern (VOCs), are associated with increase in transmissibility or virulence ( Buchan et al, 2021 ; Campbell et al, 2021 ; Tegally et al, 2021 ; Bager et al, 2021 ), decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics ( Planas et al, 2021 ; Sabino et al, 2021 ; Davis et al, 2021 ). In addition, variants of interest (VOIs) are defined as variants with specific genetic changes that are predicted or known to affect virus characteristics and identified to cause apparent epidemiological impacts to suggest an emerging risk to global public health.…”