Abstract
mRNA-based vaccines effectively induce protective neutralizing antibodies against SARS-CoV-2, the etiological agent of COVID-19. Yet, the kinetics and compositional patterns of vaccine-induced antibody responses to the original strain and emerging variants of concern remain largely unknown. Here we characterized serum antibody classes and subclasses targeting the spike receptor-binding domain of SARS-CoV-2 wild type and α, β, γ and δ variants in a longitudinal cohort of SARS-CoV-2 naïve and COVID-19 recovered individuals receiving the mRNA-1273 vaccine. We found that mRNA-1273 vaccine recipients developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by natural infection. Importantly, these antibody responses targeted both wild type SARS-CoV-2 as well as its α, β, γ and δ variants. Following primary vaccination, individuals with pre-existing immunity showed higher induction of all antibodies but IgG3 compared to SARS-CoV-2-naïve subjects. Unlike naïve individuals, COVID-19 recovered subjects did not mount a recall antibody response upon the second vaccine dose. In these individuals, secondary immunization resulted in a slight reduction of IgG1 against the receptor-binding domain of β and γ variants. Despite the lack of recall humoral response, vaccinees with pre-existing immunity still showed higher titers of IgG1 and IgA to all variants analyzed compared to fully vaccinated naïve individuals. Our findings indicate that mRNA-1273 vaccine triggered cross-variant antibody responses with distinct profiles in vaccinees with or without pre-existing immunity and suggest that individuals with prior history of SARS-CoV-2 infection may not benefit from the second mRNA vaccine dose with the current standard regimen.
Highlights
Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the leading strategy to achieve protection against coronavirus disease 19 (COVID-19) [1]
Sera were collected at three time points: pre-vaccine baseline (B), 2/3 weeks post the first dose (PFD), and one month post the second dose (PSD; Figure 1B)
As previously shown [7, 14], a higher proportion of COVID-19 recovered subjects reported side effects after the first dose of Moderna messenger RNA (mRNA) vaccine compared to naïve individuals (Supplementary Figure 1A)
Summary
Vaccination against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the leading strategy to achieve protection against coronavirus disease 19 (COVID-19) [1]. Following the first vaccine dose, COVID-19 recovered individuals show significantly higher Sand RBD-specific IgG titers, superior serum neutralization activity [7, 12,13,14], and increased S protein-specific memory T and B cell responses than naïve individuals [4,5,6, 15]. This enhanced response is consistent with the persistence of humoral and cellular immunity against SARS-CoV-2 in convalescent individuals, as previously reported [16,17,18,19,20]
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