Humoral responses to SARS-CoV-2 mRNA vaccines: Role of past infection

Abstract

Two mRNA vaccines (BNT162b2 and mRNA-1273) against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) are globally authorized as a two-dose regimen. Understanding the magnitude and duration of protective immune responses is vital to curbing the pandemic. We enrolled 461 high-risk health services workers at the University of California, Los Angeles (UCLA) and first responders in the Los Angeles County Fire Department (LACoFD) to assess the humoral responses in previously infected (PI) and infection naïve (NPI) individuals to mRNA-based vaccines (BNT162b2/Pfizer- BioNTech or mRNA-1273/Moderna). A chemiluminescent microparticle immunoassay was used to detect antibodies against SARS-CoV-2 Spike in vaccinees prior to (n = 21) and following each vaccine dose (n = 246 following dose 1 and n = 315 following dose 2), and at days 31-60 (n = 110) and 61-90 (n = 190) following completion of the 2-dose series. Both vaccines induced robust antibody responses in all immunocompetent individuals. Previously infected individuals achieved higher median peak titers (p = 0.002) and had a slower rate of decay (p = 0.047) than infection-naïve individuals. mRNA-1273 vaccinated infection-naïve individuals demonstrated modestly higher titers following each dose (p = 0.005 and p = 0.029, respectively) and slower rates of antibody decay (p = 0.003) than those who received BNT162b2. A subset of previously infected individuals (25%) required both doses in order to reach peak antibody titers. The biologic significance of the differences between previously infected individuals and between the mRNA-1273 and BNT162b2 vaccines remains uncertain, but may have important implications for booster strategies.

Fig 1. Longitudinal immune response to anti-Spike IgG following each vaccination dose and up to 90 days post-vaccination.

Anti-Spike IgG from prior to vaccination to 90 days after completion of the vaccine schedule for participants who received BNT162b2 (blue) and mRNA-1273 (red) by prior infection status (+/-) demonstrate higher levels of anti-Spike IgG in participants with prior infection. Panel A shows participants with prior infection and their anti-Spike IgG level prior to vaccination. Panels B-E show participants with and without prior infection by vaccine type. Participants with prior infection were combined regardless of vaccine type. Anti-Spike IgG levels are shown following the 1^st dose (Panel B), following the 2^nd dose (Panel C), and 31–60 days (Panel D) and 61–90 days after completion (Panel E) of the 2-dose series. Positive anti-Spike IgG titers were defined as at or above the lower limit of quantification (LLQ). High level anti-Spike IgG responses were defined at or above 3,950 AU/mL. Horizontal black lines indicate median titer level within each group. P-values compare anti-Spike IgG titers for participants with prior infection versus no prior infection and for participants with no prior infection by vaccine type, * p < 0.05 and ** p < 0.01, ***p <0.001, n.s. = not significant. There were two participants on immunosuppressive medications who did not respond to vaccination (the blue dots at or below the LLQ in panels C, D, and E). Their data is shown but not included in the analyses.

Fig 2. Anti-Spike IgG antibody dynamics and decay up to 90 days post-vaccination.

Anti-Spike IgG dynamics and decay in previously infected (solid line, filled circles) versus not previously infected (dashed line, open circles) participants by vaccine type (BNT162b2 in blue, mRNA-1273 in red), as well as slower rate of antibody decay in previously infected individuals (Panel B) and in not previously infected individuals following vaccination with mRNA-1273. Panel A demonstrates the more rapid rise of antibody titers in PI Individuals following the first dose. Anti-Spike IgG titer is displayed by time before and after the second vaccine dose (vertical black line). Blue and red arrows mark the approximate timing of the 1^st vaccine dose for BNT162b2 and mRNA-1273, respectively. Panel B and C shows the anti-Spike IgG decay after the peak is reached following the 2^nd vaccine dose. The rate of decay is slower in PI (N = 12) versus NPI (N = 168) (Panel B) and in recipients of mRNA-1273 (N = 30) versus BNT162b2 (N = 138) (Panel C).