Study examines neutralising antibody activity against SARS-CoV-2 B.1.617.2 and B.1.351 variants by BNT162b2 vaccination

Junio 4, 2021

Findings from a study published in The Lancet show that peak neutralising antibodies titres (NAbTs) were "significantly reduced" against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Variants of Concern (VOCs) B.1.617.2 (Delta variant) and B.1.351 (Beta variant) compared with NAbTs against earlier variants among individuals who received the BNT162b2 (Pfizer–BioNTech) vaccine.

"The SARS-CoV-2 B.1.617.2 VOC, first detected in India, is now dominant in the UK, having rapidly displaced the B.1.1.7 strain [Alpha variant] that emerged in the UK with the second COVID-19 wave in late 2020. The efficacy of currently licensed COVID-19 vaccines against B.1.617.2 is unknown," wrote Emma C Wall, Francis Crick Institute, London, United Kingdom, and colleagues. 

To determine vaccine-induced neutralising antibody (NAb) escape by B.1.617.2 and compare activity to previous strains with existing estimates for population-based vaccine efficacy, researchers carried out an initial analysis involving 250 participants (median age 42 years) who received the BNT162b2 vaccine. 

Using a high-throughput live-virus SARS-CoV-2 neutralisation assay, researchers determined neutralising antibodies titres (NAbTs) in 149 participants after receiving one dose of vaccine (median time after first dose=30 days [IQR 23–38]) or 159 participants after receiving two doses of vaccine (median time after second dose=28 days [IQR 21–37]) against five SARS-CoV-2 strains: a strain with the original spike sequence (Wild-type); a strain with an Asp614Gly mutation isolated during the first wave of infection in the UK in 2020 (D614G); and VOCs B.1.617.2, B.1.351 (first detected in South Africa), and B.1.1.7.

The researchers found that 2 doses of BNT162b2 elicited ELISA-detected anti-Wild-type spike antibodies in all participants, and NAb activity against all strains, including the three VOCs tested, in all except 6 (4%) and 9 (6%) of 159 participants who lacked NAb activity against B.1.617.2 and B.1.351, respectively. It was observed that NAbTs were 5.8-fold reduced against B.1.617.2 relative to Wild-type (95% confidence interval [CI] 5.0–6.9), significantly more reduced than against B.1.1.7 (2.6-fold vs Wild-type, 95% CI 2.2–3.1), and on a similar order to the reduction observed against B.1.351 (4.9-fold vs Wild-type, 95% CI 4.2–5.7).

Across all variants, the researchers observed that increased age significantly correlated with reduced NAbT (−0.33<RS<–0.27; 2.2 × 10⁻⁵<P<5.6 × 10⁻⁴), whereas no correlation was observed for sex or body-mass index. 

Among the 14 participants who attended an additional study visit 8–16 weeks after their second BNT162b2 dose, study data showed significantly reduced NAbTs against all variants (0.0002<P<0.0134). While the final NAbTs against Wild-type, D614G, and B.1.1.7 remained within the quantitative range of the assay (IC50>40), two participants' NAbTs against VOCs B.1.617.2 and B.1.351 dropped below 40 on their later study visit about 3 months after their second BNT162b2 dose.

Further, the researchers found that neutralisation of VOCs was markedly different after only one dose of BNT162b2. The researchers noted that the downwards shift in titres was significant when compared to B.1.1.7 for B.1.351 (P = 3.7 × 10⁻⁴) and B.1.617.2 (P = 1.2 × 10⁻⁵), confirming reduced NAb activity against B.1.617.2 relative to the present B.1.1.7 strain after one vaccine dose. It was also observed that participants with low NAbTs tend to be older than those who produced medium or high responses, and logistical regression analysis suggested age was a significant factor in reduced NAbTs, independent of strain (P = 0.006), following a single dose of BNT162b2.

"These data, together with epidemiological data of B.1.617.2 growth, raise the possibility that this VOC presents a dual challenge of reduced vaccine efficacy akin to the B.1.351 VOC, and increased transmissibility beyond the B.1.1.7 VOC," the authors wrote. "The impact of such a change is challenging to predict: it remains difficult to assess precisely to what extent the reduction in NAbTs we observe will impact vaccine efficacy and increase disease severity in a vaccinated population, especially given the multiple factors that contribute to this process, such as long-lived humoral immunity."

"In the case of single-dose recipients, our data show that NAbTs are significantly lower against B.1.617.2 and B.1.351 VOCs relative to B.1.1.7, implying that although a single dose might still afford considerably more protection than no vaccination, single-dose recipients are likely to be less protected against these SARS-CoV-2 variants," the authors remarked. "These data therefore suggest that the benefits of delaying the second dose, in terms of wider population coverage and increased individual NAbTs after the second dose, must now be weighed against decreased efficacy in the short-term, in the context of the spread of B.1.617.2."

"In the longer term, we note that both increased age and time since the second dose of BNT162b2 significantly correlate with decreased NAb activity against B.1.617.2 and B.1.351—both of which are also characteristic of the population in the UK at highest risk of severe COVID-19 (ie, older and vaccinated earlier), independent of other existing factors such as compromised immune status or comorbidity, or geographic-specific responses to vaccination," the authors added.

"Consequently, further booster immunisations of Joint Committee on Vaccination and Immunisation Priority Groups in the UK and similar groups in other countries, as well as others with lower vaccine-induced NAbTs than the cohort of BNT162b2 recipients studied here (ideally with modified vaccines that induce NAbs that broadly neutralise emerging VOCs) are more likely to be required to maintain the highest levels of NAbs in regions where B.1.617.2 or other equally NAb-resistant strains become prevalent," the authors noted.

Reference: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01290-3/fulltext