Poster Presentation Lorne Infection and Immunity 2023

Repeat immunisations to SARS-CoV-2 progressively increase recognition of Spike RBD-specific memory B cells to Omicron subvariants (#208)

Gemma E. Hartley 1 , Holly Fryer 1 , Emily S.J. Edwards 1 , Nirupama Varese 2 , Irene Boo 3 , Scott Bornheimer 4 , P. Mark Hogarth 2 , Heidi E. Drummer 3 , Robyn E. O'Hehir 1 5 , Menno C. van Zelm 1 5
  1. Immunology and Pathology, Monash University, Melbourne, VIC, Australia
  2. Immune Therapies Group, Burnet Institute, Melbourne, VIC, Australia
  3. Viral Entry and Vaccines Group, Burnet Institute, Melbourne, Victoria, Australia
  4. BD Biosciences, San Jose, California, USA
  5. Allergy, Asthma and Clinical Immunology, Alfred Health, Melbourne, VIC, Australia

Background:

SARS-CoV-2 vaccination coverage is increasing worldwide; however, emerging Omicron subvariants challenge its protection. Booster vaccinations improve protection against severe disease from Omicron, but the underlying mechanism is currently unknown. We assessed the capacity of vaccine-induced antibodies and circulating memory B cells (Bmem) to recognize SARS-CoV-2 Omicron subvariants.

Methods:

Recombinant Nucleocapsid protein (NCP) and Spike receptor binding domain (RBD) from Wuhan and Omicron BA.2 an BA.5 subvariants were produced for ELISA-based serology, and biotinylated for fluorescent tetramer formation to identify RBD-specific Bmem by flow cytometry. Healthy adults vaccinated with the Pfizer mRNA (n=30) or AstraZeneca vector (n=35) vaccinations were sampled before and 1 month after 1st and 2nd dose immunisation, and 3rd dose mRNA booster.

Results:

None of the participants carried IgG to NCP or RBD before vaccination. IgG to RBD progressively increased after 1st, 2nd and 3rd dose of vaccination. AstraZeneca vaccination induced significantly lower levels of RBD IgG than Pfizer vaccination. Bmem numbers after double-dose vaccination were similar for AstraZeneca and Pfizer groups. First dose Pfizer vaccination elicited RBD-specific Bmem, which expressed predominantly IgM or IgG1; the 2nd and 3rd doses expanded the IgG1+ Bmem numbers. The proportions of RBD-specific Bmem recognizing Omicron BA.2 or BA.5 increased from ~20% to >40% after 3 vaccine doses.

Conclusions:

Double-dose Pfizer mRNA and AstraZeneca vector vaccinations generate RBD-specific antibodies with significant loss in recognition of Omicron subvariants. The 2nd vaccine dose as well as 3rd dose mRNA boosters progressively increase the capacity of RBD-specific Bmem to recognize Omicron subvariants. This suggests that the additional exposures elicit affinity maturation of RBD-specific Bmem thereby overcoming mismatches in variant RBD. In ongoing studies, we will evaluate the impact of the bivalent 4th dose booster vaccine (Wuhan and Omicron BA.1) on Bmem recognition of Omicron subvariants.