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. 2024 May 15:15:1401209.
doi: 10.3389/fimmu.2024.1401209. eCollection 2024.

Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response

Ryan Baker Jr  1 , Rebecca Lawlor  1 , Maeve Smith  1 , Jessica Price  1 , Ashley Eaton  2 , Andrew Lover  3 , Dominique Alfandari  1 , Peter Reinhart  4 , Kathleen F Arcaro  1 , Barbara A Osborne  1
Affiliations

Antibody responses in blood and saliva post COVID-19 bivalent booster do not reveal an Omicron BA.4/BA.5- specific response

Ryan Baker Jr et al. Front Immunol. .

Abstract

Introduction: Current SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.4 and BA.5 variants.

Methods: We recruited volunteers from University of Massachusetts student, faculty and staff members to provide samples of blood and saliva at four different time points, including pre-boost and three times post boost and analyzed samples for antibody production as well as neutralization of virus.

Results: Our data provide a comprehensive analysis of the antibody response following a single dose of the bivalent boost over a 6-month period and support previous findings that the response induced after the bivalent boost does not create a strong BA.4/BA.5-specific antibody response.

Conclusion: We found no evidence of a specific anti-BA.4/BA.5 response developing over time, including in a sub-population of individuals who become infected after a single dose of the bivalent booster. Additionally, we present data that support the use of saliva samples as a reliable alternative to blood for antibody detection against specific SARS-CoV-2 antigens.

Keywords: COVID - 19; ELISA; antibody response; dried blood spot cards; neutralization assay; saliva.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Overview of participant enrollment and sample collection. Created with BioRender.com.
Figure 2
Figure 2
RBD binding and virus neutralization increases after boost. Antibody responses against ancestral Wuhan-Hu-1 strain (red) and the Omicron BA.4/BA.5 variant (blue) are shown. Individual IgG concentrations and 50% neutralizing titer (NT50) detected in blood eluates against Wuhan-Hu-1 pseudo-virus (A), and against the Omicron BA.4/BA.5 variant (B). The IgG levels from saliva also are shown against both variants (C). Solid colored lines represent geometric means in the respective sample set of each timepoint. Sample populations are as follows:to Pre N=80, Post 1 N=81, Post 2 n=61, Post 3 n=46. ns, not significant; * <0.05; ***p <0.001; Wilcoxon matched-pairs signed rank test assuming non-Gaussian distribution.
Figure 3
Figure 3
Wuhan-Hu-1 antibody response is greater than that of Omicron BA.4/BA.5. Comparison of the antibody response to the Wuhan-Hu-1 strain with the Omicron variant (A): IgG concentrations in DBS eluates (upper), NT50s of DBS eluates (middle), and IgG concentrations in saliva (lower). The percentage of the anti-Omicron BA.4/BA.5 IgG (blue) from the total-RBD-IgG in blood eluates (B) and saliva (C). ***p<0.001; Mann-Whitney test.
Figure 4
Figure 4
Antibody responses in individuals testing positive for COVID-19 after the bivalent boost provide support for immune imprinting. Antibody (IgG) responses measured in DBS eluates against ancestral Wuhan-Hu-1 strain (A) and Omicron BA.4/BA.5 strain (B) for the seven individuals who tested positive for COVID-19 after receiving the bivalent boost. Individual IgG changes over time (left) and levels of 50% neutralizing titer (NT50) against respective pseudo-virus (right) are shown. Sample populations are as follows: Pre & Post 1 n=7, Post 2 n=5, Post 3 n=6. Part of whole graphs (C) show percentage of anti-Omicron BA.4/BA.5 IgG (blue) in blood eluate out of total-RBD-IgG in individuals testing positive for COVID-19 post-bivalent boost. (D) The XBB Omicron variant replaced BA.5 Omicron as the most prevalent SARS-CoV-2 variant on the UMass, Amherst, Campus beginning in January 2023. SARS-CoV-2 variant percentages calculated from whole-genome sequencing (WGS) results are shown.
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