Impact of SARS-CoV-2 infection on vaccine-induced immune responses over time

Abstract

Objective: To determine the long-term impact of prior SARS-CoV-2 infection on immune responses after COVID-19 vaccination.

Methods: Using longitudinally collected blood samples from the COMMUNITY study, we determined binding (WHO BAU mL^-1) and neutralising antibody titres against ten SARS-CoV-2 variants over 7 months following BNT162b2 in SARS-CoV-2-recovered (n = 118) and SARS-CoV-2-naïve (n = 289) healthcare workers with confirmed prior SARS-CoV-2 infection. A smaller group with (n = 47) and without (n = 60) confirmed prior SARS-CoV-2 infection receiving ChAdOx1 nCoV-19 was followed for 3 months. SARS-CoV-2-specific memory T-cell responses were investigated in a subset of SARS-CoV-2-naïve and SARS-CoV-2-recovered vaccinees.

Results: Vaccination with both vaccine platforms resulted in substantially enhanced T-cell responses, anti-spike IgG responses and neutralising antibodies effective against ten SARS-CoV-2 variants in SARS-CoV-2-recovered participants as compared to SARS-CoV-2-naïve participants. The enhanced immune responses sustained over 7 months following vaccination.

Conclusion: These findings imply that prior SARS-CoV-2 infection should be taken into consideration when planning booster doses and design of current and future COVID-19 vaccine programmes.

Keywords: COVID‐19; SARS‐CoV‐2; hybrid immunity; immune responses; vaccination.

Figure 1

Timeline for vaccination and sample collection. The cohort (n = 514) is divided into participants receiving BNT162b2 with a 3‐ to 4‐week (n = 335) and 6‐ to 8‐week (n = 72) dose interval and ChAdOx1 nCoV‐19 (n = 107) with a 10‐ to 12‐week dose interval. Blue characters represent vaccinees who received BNT162b2, and yellow characters represent vaccinees who received ChAdOx1 nCoV‐19. Light‐coloured characters represent SARS‐CoV‐2 naïve, and dark‐coloured characters represent participants with SARS‐CoV‐2 infection prior to vaccination. Test tubes represent time for blood sampling, and syringes represent time for vaccination. W, weeks; d.i., dose interval.

Figure 2

Binding and pseudo‐neutralising antibody titres over time following BNT162b2 and ChAdOx1 nCoV‐19 vaccination with and without prior SARS‐CoV‐2 infection. (a) Binding antibody titres against SARS‐CoV‐2 wild type over 7 months following the second BNT162b2 dose (n = 335) and 3 months following the second ChAdOx1 nCoV‐19 dose (n = 107) in SARS‐CoV‐2‐recovered and SARS‐CoV‐2‐naïve vaccinees, (b) pseudo‐neutralising antibodies against the wild type over 7 months following the second BNT162b2 dose (n = 312) and 3 months following the second ChAdOx1 nCoV‐19 dose (n = 100) in SARS‐CoV‐2‐recovered and SARS‐CoV‐2‐naïve vaccinees, and (c) pseudo‐neutralising antibodies against the Delta variant type over 7 months following the second BNT162b2 dose (n = 312) and 3 months following the second ChAdOx1 nCoV‐19 dose (n = 100) in SARS‐CoV‐2‐recovered and SARS‐CoV‐2‐naïve vaccinees. Dots and crosses represent GMTs, and bars represent 95% CI. Solid lines represent SARS‐CoV‐2‐recovered vaccinees, and dotted lines represent SARS‐CoV‐2‐naïve vaccinees. WT, wild type; BAU, binding antibody units; AU, arbitrary units.

Figure 3

Impact of an additional 3‐month interval between infection (confirmed seroconversion) and vaccination on vaccine‐induced binding and neutralising antibody titres. Effect estimates on binding (blue squares) and neutralising (red squares) on antibody titres against ten SARS‐CoV‐2 variants including SARS‐CoV‐2 wild‐type (A (WT)) and B.1.1.7 (Alpha), B.1.351 (Beta), B.1.526.1 (New York), B.1.617 (India), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3 (India), P.1 (Gamma) and P.2 (Zeta) variants following BNT162b2 and ChAdOx1 nCoV‐19 vaccination. Red squares represent the factor increase in SARS‐CoV‐2 spike IgG, and blue squares represent the factor increase in SARS‐CoV‐2 pseudo‐neutralising antibodies per 3 months’ increase in the interval between infection (as defined by confirmed seroconversion) and vaccination.

Figure 4

Neutralising capacity over time. Neutralising capacity (a) 3 months (n = 227) and (b) 7 months (n = 312) post‐BNT162b2 vaccination and (c) 3 months (n = 100) post‐ChAdOx1 nCoV‐19 vaccination against ten SARS‐CoV‐2 variants including the wild‐type (WT), B.1.1.7 (Alpha), B.1.351 (Beta), B.1.526.1 (New York), B.1.617 (India), B.1.617.1 (Kappa), B.1.617.2 (Delta), B.1.617.3 (India), P.1 (Gamma) and P.2 (Zeta) variants. Dots represent GMTs, and bars represent 95% CI. Dark‐coloured dots represent SARS‐CoV‐2‐recovered vaccinees, and light‐coloured dots represent SARS‐CoV‐2‐naïve vaccinees.

Figure 5

Memory T‐cell responses three and 7 months following BNT162b2 and ChAdOx1 nCoV‐19 vaccination in SARS‐CoV‐2‐recovered and SARS‐CoV‐2‐naïve participants. (a–c) The whole‐blood IGRA using a SARS‐CoV‐2‐specific peptide pool (8 SARS‐CoV‐2‐specific peptides covering the SARS‐CoV‐2 spike protein ¹³ , ²⁸ ). (d–g) T‐cell responses against S1, S2, N and M analysed against a T‐SPOT^® Discovery SARS‐CoV‐2 kit (Oxford Immunotec, Oxfordshire, UK). The cut‐off for positivity was set at t > 40 SFU mL⁻¹. Blue dots represent BNT162b2 vaccinees (a, b, d–g), and orange dots represent ChAdOx1 nCoV‐19 vaccinees (c). Dark‐coloured dots represent SARS‐CoV‐2‐recovered (n = 9) participants, and light‐coloured dots represent SARS‐CoV‐2‐naïve (n = 8) participants. Lines represent geometric mean, and error bars represent 95% confidence interval.