Med
Volume 3, Issue 12, 9 December 2022, Pages 838-847.e3
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Clinical and Translational Report
Duration of BA.5 neutralization in sera and nasal swabs from SARS-CoV-2 vaccinated individuals, with or without omicron breakthrough infection

https://doi.org/10.1016/j.medj.2022.09.010Get rights and content
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Highlights

  • Different dynamics of Nab response against ancestral and BA.5 viral isolates.

  • Omicron breakthrough infection induces a longer lasting Nab response

  • Omicron infection, but not vaccination, triggers a Nab response at the nasal mucosae

Context and significance

Since the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant in December 2022, approximately 50% of the world population has been infected, reflecting a poor protection against infection conferred by vaccination. Researchers from Paris, France, report that, upon vaccination, the duration of an efficient antibody response was significantly shorter for Omicron variants, including BA.5, compared with the ancestral strain. After breakthrough infection, antibody levels against Omicron subvariants increased, and remained elevated for at least 5–6 months. Breakthrough infection, but not vaccination, triggered detectable local response in the nasal mucosa against SARS-CoV-2. These results show that the longitudinal survey of antibody levels in blood and nasal samples may provide a reliable marker of the effectiveness of vaccination, natural, and hybrid immunity against acquisition of current and future SARS-CoV-2 variants.

Summary

Background

Since early 2022, Omicron BA.1 has been eclipsed by BA.2, which was in turn outcompeted by BA.5, which displays enhanced antibody escape properties.

Methods

Here, we evaluated the duration of the neutralizing antibody (Nab) response, up to 18 months after Pfizer BNT162b2 vaccination, in individuals with or without BA.1/BA.2 breakthrough infection. We measured neutralization of the ancestral D614G lineage, Delta, and Omicron BA.1, BA.2, and BA.5 variants in 300 sera and 35 nasal swabs from 27 individuals.

Findings

Upon vaccination, serum Nab titers were decreased by 10-, 15-, and 25-fold for BA.1, BA.2, and BA.5, respectively, compared with D614G. We estimated that, after boosting, the duration of neutralization was markedly shortened from 11.5 months with D614G to 5.5 months with BA.5. After breakthrough, we observed a sharp increase of Nabs against Omicron subvariants, followed by a plateau and a slow decline after 5–6 months. In nasal swabs, infection, but not vaccination, triggered a strong immunoglobulin A (IgA) response and a detectable Omicron-neutralizing activity.

Conclusions

BA.5 spread is partly due to abbreviated vaccine efficacy, particularly in individuals who were not infected with previous Omicron variants.

Funding

Work in O.S.’s laboratory is funded by the Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, Fondation pour la Recherche Médicale (FRM), ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, ANR Coronamito, and IDISCOVR, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant no. ANR-10-LABX-62-IBEID), HERA european funding and the NIH PICREID (grant no U01AI151758).

Keywords

SARS-Cov-2
variants
Omicron
BA.5
neutralization
vaccine
breakthrough
mucosal immunity
IgG
IgA

CAT scale

Translation to patients

Data and code availability

  • SARS-CoV-2 variants genomes have been deposited at GISAID and are publicly available as of the date of publication. Accession numbers are listed in the key resources table.

  • This study did not generate any new codes.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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