SARS-CoV-2 BA.1 variant is neutralized by vaccine booster–elicited serum but evades most convalescent serum and therapeutic antibodies

Abstract

The rapid spread of the highly contagious Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) along with its high number of mutations in the spike gene has raised alarms about the effectiveness of current medical countermeasures. To address this concern, we measured neutralization of the Omicron BA.1 variant pseudovirus by post-vaccination serum samples after two and three immunizations with the Pfizer/BioNTech162b2 SARS-CoV-2 mRNA (Pfizer/BNT162b2) vaccine, convalescent serum samples from unvaccinated individuals infected by different variants, and clinical-stage therapeutic antibodies. We found that titers against the Omicron variant were low or undetectable after two immunizations and in many convalescent serum samples, regardless of the infecting variant. A booster vaccination increased titers more than 30-fold against Omicron to values comparable to those seen against the D614G variant after two immunizations. Neither age nor sex were associated with differences in post-vaccination antibody responses. We also evaluated eighteen clinical-stage therapeutic antibody products and an antibody mimetic protein product obtained directly from the manufacturers. Five monoclonal antibodies, the antibody mimetic protein, three antibody cocktails, and two polyclonal antibody preparations retained measurable neutralization activity against Omicron with a varying degree of potency. Of these, only three retained potencies comparable to the D614G variant. Two therapeutic antibody cocktails in the tested panel that are authorized for emergency use in the United States did not neutralize Omicron. These findings underscore the potential benefit of mRNA vaccine boosters for protection against Omicron and the need for rapid development of antibody therapeutics that maintain potency against emerging variants.

COVID-19 Vaccine effectiveness against symptomatic infection and hospitalization in Belgium, July 2021-APRIL 2022

“…We demonstrated that a more recent infection was associated with higher protection. This likely indicates both waning of infection- acquired immunity and differences in cross-neutralization between VOCs [35]. Given the functional relevance of immunological processes such as cross-neutralization and affinity maturation [11,36], observed time trends in convalescents are specific to the sequence of VOCs.…”

Resistance of SARS-CoV-2 Omicron BA.1 and BA.2 Variants to Vaccine-Elicited Sera and Therapeutic Monoclonal Antibodies

“…The highly transmissible variant further mutated to generate sublineages BA.1, BA.2, BA.3, BA.4, and BA.5, with BA.1 and BA.2 responsible for most transmissions worldwide. Although BA.1 and BA.2 are less pathogenic [2][3][4][5][6], BA.1 evades antibody neutralization by the sera of vaccinated donors and escapes neutralization by most of the emergency use authorized therapeutic monoclonal antibodies [7][8][9][10][11][12][13][14][15][16]. BA.2 is 1.5-fold more transmissible than BA.1 and is currently the prevalent variant in the United States (85.9% as of 9 April 2022) [17].…”

VH3-53/66-Class RBD-Specific Human Monoclonal Antibody iB20 Displays Cross-Neutralizing Activity against Emerging SARS-CoV-2 Lineages

“…Of thousands of SARS-CoV-2-specific nAbs identified to date, only a small proportionare known to neutralize the Omicron variant of SARS-CoV-2 [ 6 , 7 , 8 , 18 ]. Typically, they do so at a higher concentration, compared to the neutralization of earlier viral variants.…”

“…The VH1-58 class representatives that displayed potent cross-neutralization against all pre-Omicron SARS-CoV-2 variants [ 9 , 10 , 11 ] have largely failed against Omicron [ 6 , 8 , 18 , 20 ]. iB14, identified and characterized earlier by our group, was no exception, and displayed a 20- to 50-fold reduced neutralization potency against authentic Omicron or Omicron S-pseudotypedlentiviral particles compared to the B.1 variant.…”