Neutralization of SARS-CoV-2 Omicron sublineages by 4 doses of the original mRNA vaccine

Xuping Xie, Jing Zou, Chaitanya Kurhade, Mingru Liu, Ping Ren, Shi Pei-Yong Shi

Research output: Contribution to journalArticlepeer-review


Since the initial emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.1, several Omicron sublineages have emerged, leading to BA.5 as the current dominant sublineage. Here, we report the neutralization of different Omicron sublineages by human sera collected from individuals who had distinct mRNA vaccination and/or BA.1 infection. Four-dose-vaccine sera neutralize the original USA-WA1/2020, Omicron BA.1, BA.2, BA.2.12.1, BA.3, and BA.4/5 viruses with geometric mean titers (GMTs) of 1,554, 357, 236, 236, 165, and 95, respectively; two-dose-vaccine-plus-BA.1-infection sera exhibit GMTs of 2,114, 1,705, 730, 961, 813, and 274, respectively; and three-dose-vaccine-plus-BA.1-infection sera show GMTs of 2,962, 2,038, 983, 1,190, 1,019, and 297, respectively. Thus, the four-dose vaccine elicits the lowest neutralization against BA.5; the two-dose vaccine plus BA.1 infection elicits significantly higher GMTs against Omicron sublineages than the four-dose-vaccine; and the three-dose vaccine plus BA.1 infection elicits slightly higher GMTs (statistically insignificant) than the two-dose vaccine plus BA.1 infection. Finally, the BA.2.75 is more susceptible than BA.5 to four-dose-vaccine-elicited neutralization and three-dose-vaccine-plus-BA.1-infection-elicited neutralization.

Original languageEnglish (US)
Article number111729
JournalCell Reports
Issue number9
StatePublished - Nov 29 2022


  • CP: Immunology
  • CP: Microbiology
  • SARS-CoV-2
  • breakthrough
  • mRNA vaccine
  • neutralization
  • variants

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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