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Omicron sub-lineages BA.4/BA.5 escape BA.1 infection elicited neutralizing immunity

2022; Cold Spring Harbor Laboratory; Linguagem: Inglês

10.1101/2022.04.29.22274477

Khadija Khan, Farina Karim, Yashica Ganga, Mallory Bernstein, Zesuliwe Jule, Kajal Reedoy, Sandile Cele, Gila Lustig, Daniel G. Amoako, Nicole Wolter, Natasha Samsunder, Aida Sivro, James Emmanuel San, Jennifer Giandhari, Houriiyah Tegally, Sureshnee Pillay, Yeshnee Naidoo, Matilda Mazibuko, Yoliswa Miya, Nokuthula Ngcobo, Nithendra Manickchund, Nombulelo Magula, Quarraisha Abdool Karim, Anne von Gottberg, Salim S. Abdool Karim, Willem A. Hanekom, Bernadett I. Gosnell, Richard Lessells, Túlio de Oliveira, Mahomed‐Yunus S. Moosa, Alex Sigal,

Animal Virus Infections Studies

The SARS-CoV-2 Omicron (B.1.1.529) variant first emerged as the BA.1 sub-lineage, with extensive escape from neutralizing immunity elicited by previous infection with other variants, vaccines, or combinations of both 1,2 . Two new sub-lineages, BA.4 and BA.5, are now emerging in South Africa with changes relative to BA.1, including L452R and F486V mutations in the spike receptor binding domain. We isolated live BA.4 and BA.5 viruses and tested them against neutralizing immunity elicited to BA.1 infection in participants who were Omicron/BA.1 infected but unvaccinated (n=24) and participants vaccinated with Pfizer BNT162b2 or Johnson and Johnson Ad26.CoV.2S with breakthrough Omicron/BA.1 infection (n=15). In unvaccinated individuals, FRNT 50 , the inverse of the dilution for 50% neutralization, declined from 275 for BA.1 to 36 for BA.4 and 37 for BA.5, a 7.6 and 7.5-fold drop, respectively. In vaccinated BA.1 breakthroughs, FRNT 50 declined from 507 for BA.1 to 158 for BA.4 (3.2-fold) and 198 for BA.5 (2.6-fold). Absolute BA.4 and BA.5 neutralization levels were about 5-fold higher in this group versus unvaccinated BA.1 infected participants. The observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity 1,3 . However, the low absolute neutralization levels for BA.4 and BA.5, particularly in the unvaccinated group, are unlikely to protect well against symptomatic infection 4 .This may indicate that, based on neutralization escape, BA.4 and BA.5 have potential to result in a new infection wave.