NGS-SA: Publications and pre-prints of our genomics surveillance work

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection.

Authors: Khan K, Karim F, Ganga Y, Bernstein M, Jule Z, Reedoy K, Cele S, Lustig G, Amoako D, Wolter N, Samsunder N, Sivro A, San JE, Giandhari J, Tegally H, Pillay S, Naidoo Y, Mazibuko M, Miya Y, Ngcobo N, Manickchund N, Magula N, Karim QA, von Gottberg A, Abdool Karim SS, Hanekom W, Gosnell BI; COMMIT-KZN Team, Lessells RJ, de Oliveira T, Moosa MS, Sigal A

Journal: Nature Communications, 2022. DOI:


SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vaccination as well as from vaccination without BA.1 infection. In BA.1-infected unvaccinated individuals, neutralization relative to BA.1 declines 7.6-fold for BA.4 and 7.5-fold for BA.5. In vaccinated individuals with subsequent BA.1 infection, neutralization relative to BA.1 decreases 3.2-fold for BA.4 and 2.6-fold for BA.5. The fold-drop versus ancestral virus neutralization in this group is 4.0-fold for BA.1, 12.9-fold for BA.4, and 10.3-fold for BA.5. In contrast, BA.4/BA.5 escape is similar to BA.1 in the absence of BA.1 elicited immunity: fold-drop relative to ancestral virus neutralization is 19.8-fold for BA.1, 19.6-fold for BA.4, and 20.9-fold for BA.5. These results show considerable escape of BA.4/BA.5 from BA.1 elicited immunity which is moderated with vaccination and may indicate that BA.4/BA.5 may have the strongest selective advantage in evading neutralization relative to BA.1 in unvaccinated, BA.1 infected individuals.