The race to produce vaccines against SARS-CoV-2 began when the first sequence was published, and this forms the basis for vaccines currently deployed globally.
Independent lineages of SARS-CoV-2 have recently been reported: UK–B.1.1.7, South Africa–B.1.351 and Brazil–P.1. These variants have multiple changes in the immunodominant spike protein which facilitates viral cell entry via the Angiotensin converting enzyme-2 (ACE2) receptor.
Mutations in the receptor recognition site on the spike are of great concern for their potential for immune escape.
This paper publishe on Cell by University of Oxford researchers describes a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes.
In this manuscript, it’s demonstrated that the B.1.351 CoV-2 strain is much more difficult to neutralize than parental strains, 14/20 of a panel of monoclonal antibodies are seriously compromised or neutralization is completely knocked out. On convalescent serum the neutralization titres are reduced 13.3-fold for B.1.351 compared with the Victoria strain with 14/34 failing to reach an NT50 at a 1:20 dilution and a number showing almost complete knock down of activity.
It remains to be determined if this reflects a focussing of the immune
response in these individuals, as has been seen, for instance for the picornavirus enterovirus.
Neutralization titres for the Oxford-AstraZeneca and Pfizer vaccines were similarly reduced with B.1.351 by 9 and 7.6-fold respectively.
For the Oxford AstraZeneca vaccine when compared to the Pfizer vaccine, more sera failed to reach FRNT50 at 1:20 dilution and, since the reduction in FRNT50 titres between the two vaccines were quite similar, this effect was due to the 3.6-fold lower starting titres for the Oxford-AstraZenca
vaccine versus the Pfizer-BioNTech vaccine. However, both the Oxford-AstraZeneca and Pfizer vaccines give substantial initial efficacy after a single dose of vaccine against parental strains (~76% and 89% respectively), implying neutralizing antibody titres required for this level of protection are modest.
Very recent data suggests that the Novavax vaccine, which achieved 95.6% efficacy against previous SARS-CoV-2 strains and 85.6% against B.1.1.7 in the UK had reduced efficacy of 60% in South Africa, where 92.6% of infections are estimated to have been B.1.351.
Furthermore, data from the Novavax trial in South Africa (2021), indicates that approximately 1/3 of the study participants were seropositive at enrolment however, in the placebo arm of the study there was no difference in the rate of infection in seronegative versus seropositive volunteers (3.9% vs 3.9%), implying a lack of protection of previous SARS-CoV-2 exposure to infection with B.1.351.
The Janssen single dose COVID-19 vaccine showed 72% efficacy at preventing moderate and severe disease, which was reduced to 57% in South Africa.
Finally, a recent report from South Africa on a small sample size suggests substantial loss of efficacy for the Oxford-Astrazeneca vaccine against B.1.351 infection (10.6% efficacy against mild-moderate disease).
There are no reports yet of the efficacy of the Pfizer-BioNTech vaccine against B.1.351 however, the neutralization titres reported here suggest that a degree of efficacy will be retained. Overall,
These results suggest that previous infection or vaccination with ancestral strains of SARS448 CoV-2 may not provide adequate protection against B.1.351.
In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.