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An extended interval between vaccination and infection enhances hybrid immunity against SARS-CoV-2 variants
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
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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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 4

Exposure interval determines strength of hybrid immunity.

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Exposure interval determines strength of hybrid immunity.
Comparison of ...
Comparison of exposure interval, the time between first and last antigen exposure, with (A) full-length spike EC50 antibody levels and neutralization of (B) WA1, (C) Alpha, (D) Beta, (E) Delta, (F) Omicron (BA.1), and (G) Omicron (BA.2). (H) Neutralization of variants binned by exposure interval in days. (I) Heatmap of correlation significance between explanatory and response variables. Individual values in A–G are shown as filled circles, and the shaded area indicates the linear fit with 95% CI. R2 is indicated for each curve fit. P values in A–G show the result of an F test using a 0-slope null hypothesis. P values in H show the result of Mann-Whitney U tests with the Holm-Šídák multiple comparison correction. Colors in I represent the P values of Pearson’s r correlation coefficients according to the scale bar. All P values are 2 tailed, and P = 0.05 was considered significant. For A–G and I, n = 46. For H, n = 7 for the 35–100 days group, n = 10 for the 101–200 days group, n = 18 for the 201–300 days group, and n = 11 for the 301–404 days group.

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