Study population and setting
This in vitro study assessed the susceptibility of the B.1.351 SARS-CoV-2 variant to sera from 10 convalescent donors who had recovered from COVID-19 and who had received a single dose of the Pfizer (n=7) or Moderna (n=3) mRNA SARS-CoV-2 vaccine. Responses were assessed before vaccination (median 202 days after symptom onset) and after vaccination (median 16 days later). The authors also assessed neutralizing activity of monoclonal antibodies (mAbs) from infected patients who had not been vaccinated. The B.1.351 variant, which was first observed in South Africa, is characterized by mutations in the spike protein (S) that have led to concerns over possible increased infectivity and evasion of neutralizing antibody responses. The authors evaluated neutralizing effects on: 1) pseudovirus expressing the S protein from the Wuhan Hu1 variant, which was used for encoding S protein in the mRNA vaccines; 2) pseudovirus expressing S protein with B.1.351-defining mutations; and 3) SARS-CoV-1 pseudovirus.
Summary of Main Findings
Using mAbs targeting various epitopes (in the receptor binding domain, the N-terminal domain, and the S2 subunit), the authors found lower neutralizing activity against the B.1.351 strain relative to the Wuhan Hu1 variant. Pre-vaccine sera from 9 of 10 donors weakly neutralized the Wuhan Hu1 variant, but only 5 of 10 were able to weakly neutralize the B.1.351 variant. Post-vaccine sera exhibited an approximately 1000-fold increase in neutralizing Ab response; and median neutralizing Ab titers (ID50) were nearly three times higher for the Wuhan Hu1 strain than for the B.1.351 strain (14,100 vs. 5,156, p=0.002). Although pre-vaccine sera could not neutralize SARS-CoV-1 pseudovirus, all post-vaccination sera neutralized SARS-CoV1 at titers that were approximately 100-fold lower than those neutralizing the Wuhan Hu1 variant of SARS-CoV-2.
Sera were tested for neutralizing activity both before and after vaccination, limiting potential confounding by donor characteristics. Testing for neutralizing activity against SARS-CoV-1 provides information about the breadth of immune response to more divergent strains.
Because immunological correlates of protection against SARS-CoV-2 infection are not well understood, neutralizing Ab activity in vitro against SARS-CoV-2 may not correlate well with any actual resistance to infection or severe disease. Sera from only 10 donors were assessed, with considerable variation in neutralizing titers; a larger sample would improve the ability to distinguish true differences from random variation. Because of the small sample, it was not possible to assess any differences between those receiving Pfizer and Moderna vaccines.
This provides some of the first evidence regarding immunogenicity conferred by vaccination among people with previous SARS-CoV-2 infection, particularly with respect to emerging variants of concern.
This review was posted on: 19 February 2021