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An extended interval between vaccination and infection enhances hybrid immunity against SARS-CoV-2 variants
Timothy A. Bates, … , Marcel E. Curlin, Fikadu G. Tafesse
Timothy A. Bates, … , Marcel E. Curlin, Fikadu G. Tafesse
Published January 26, 2023
Citation Information: JCI Insight. 2023;8(5):e165265. https://doi.org/10.1172/jci.insight.165265.
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Research Article COVID-19 Vaccines

An extended interval between vaccination and infection enhances hybrid immunity against SARS-CoV-2 variants

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Abstract

As the COVID-19 pandemic continues, long-term immunity against SARS-CoV-2 will be important globally. Official weekly cases have not dropped below 2 million since September of 2020, and continued emergence of novel variants has created a moving target for our immune systems and public health alike. The temporal aspects of COVID-19 immunity, particularly from repeated vaccination and infection, are less well understood than short-term vaccine efficacy. In this study, we explored the effect of combined vaccination and infection, also known as hybrid immunity, and the timing thereof on the quality and quantity of antibodies elicited in a cohort of 96 health care workers. We found robust neutralizing antibody responses among those with hybrid immunity; these hybrid immune responses neutralized all variants, including BA.2. Neutralizing titers were significantly improved for those with longer vaccine-infection intervals of up to 400 days compared with those with shorter intervals. These results indicate that anti–SARS-CoV-2 antibody responses undergo continual maturation following primary exposure by either vaccination or infection for at least 400 days after last antigen exposure. We show that neutralizing antibody responses improved upon secondary boosting, with greater potency seen after extended intervals. Our findings may also extend to booster vaccine doses, a critical consideration in future vaccine campaign strategies.

Authors

Timothy A. Bates, Hans C. Leier, Savannah K. McBride, Devin Schoen, Zoe L. Lyski, David X. Lee, William B. Messer, Marcel E. Curlin, Fikadu G. Tafesse

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Figure 3

Antibody quality and variant cross-neutralization are improved with hybrid immunity.

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Antibody quality and variant cross-neutralization are improved with hybr...
Individual neutralizing FRNT50 values against WA1 versus (A) Alpha, (B) Beta, (C) Delta, (D) Omicron (BA.1), and (E) Omicron (BA.2). Diagonal broken lines indicate equal neutralization of WA1 and variant in A–D. (F) Relative neutralization, calculated as the neutralizing titer against each of the variants divided by the neutralizing titer against WA1. (G) Neutralizing potency index, indicating the neutralizing FRNT50 against the indicated variant divided by full-length spike protein EC50 antibody levels. Vaccine-only participants are represented by red circles, and hybrid immune participants are represented by blue squares. Error bars represent the geometric mean, with 95% CIs. P values in F and G show the result of Mann-Whitney U tests with the Holm-Šídák multiple comparison correction. All P values are 2 tailed, and P = 0.05 was considered significant. For all panels, n = 20 for the vaccine-only group and n = 46 for the hybrid immunity group.

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