Abstract:The rapid development of mRNA-based vaccines against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the design of accelerated vaccination schedules that have been extremely effective in naïve individuals. While a two-dose immunization regimen with the BNT162b2 vaccine has been demonstrated to provide a 95% efficacy in naïve individuals, the effects of the second vaccine dose in individuals who have previously recovered from natural SARS-CoV-2 infection has not been investigated in deta… Show more
“…Interestingly, SARS-CoV-2 naïve individuals and individuals with prior history of infection have distinct immune responses upon mRNA vaccination. 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).…”
Section: Introductionsupporting
confidence: 85%
“…Earlier phase III trials and more recent studies have demonstrated that mRNA-1273 vaccine induces a robust IgG response against SARS-CoV-2 wild type (WT) strain and promotes the generation of S-specific memory T and B cells after the two-dose regimen (2)(3)(4)(5)(6)(7)(8). Among the different antibodies induced by vaccination, those recognizing the S protein receptorbinding domain (RBD) are particularly relevant as they mirror the serum neutralizing capacity (9,10), and are considered a main correlate of immune protection and vaccine efficacy (11).…”
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.
“…Interestingly, SARS-CoV-2 naïve individuals and individuals with prior history of infection have distinct immune responses upon mRNA vaccination. 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).…”
Section: Introductionsupporting
confidence: 85%
“…Earlier phase III trials and more recent studies have demonstrated that mRNA-1273 vaccine induces a robust IgG response against SARS-CoV-2 wild type (WT) strain and promotes the generation of S-specific memory T and B cells after the two-dose regimen (2)(3)(4)(5)(6)(7)(8). Among the different antibodies induced by vaccination, those recognizing the S protein receptorbinding domain (RBD) are particularly relevant as they mirror the serum neutralizing capacity (9,10), and are considered a main correlate of immune protection and vaccine efficacy (11).…”
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.
“…We observed that all convalescent individuals elicited a stronger humoral and cellular immunity than naïve individuals irrespective of the vaccination regime (Fig. 5A), in line with recent data (33)(34)(35).…”
Section: Characterization Of Spike-specific Humoral and Cellular Immune Responses In Vaccinated Sars-cov-2 Convalescentssupporting
Protection offered by COVID-19 vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking.
We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated individuals (n=55) who were either primed with Ad26.COV2.S only (n=13), or boosted with a homologous (Ad26.COV2.S, n=28) or heterologous (BNT162b2, n=14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n=16) or double (n=44) dose of BNT162b2. We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both, Spike-specific humoral and cellular immunity in Ad26.COV2.S vaccinated. In contrast, the impact of homologous boost was quantitatively minimal in Ad26.COV2.S vaccinated and Spike-specific antibodies and T cells were narrowly focused to the S1 region. Although a direct association between quantity and quality of immunological parameters and in vivo protection has not been demonstrated, the immunological features of Spike-specific humoral and cellular immune responses support the utilization of a heterologous strategy of vaccine boost in individuals who received Ad26.COV2.S vaccination.
“…We observed that all convalescent individuals elicited a stronger humoral and cellular immunity than naive individuals irrespective of the vaccination regime ( Figure 5 A), in line with recent data. 35 , 36 , 37 Figure 5 Spike-specific humoral and cellular immune response in convalescent vaccinated individuals Spike IgG antibody, sVNT, Spike-specific MBCs, and T cell responses were tested in five cohorts of naive vaccinated individuals: J (n = 12), J+J (n = 23), J+P (n = 9), P (n = 10), and P+P (n = 37). Same analysis was carried out in SARS-CoV-2 convalescent vaccinated individuals: J (n = 1), J+J (n = 5), P (n = 6), P+P (n = 7), and J+P (n = 5).…”
Background
Protection offered by coronavirus disease 2019 (COVID-19) vaccines wanes over time, requiring an evaluation of different boosting strategies to revert such a trend and enhance the quantity and quality of Spike-specific humoral and cellular immune responses. These immunological parameters in homologous or heterologous vaccination boosts have thus far been studied for mRNA and ChAdOx1 nCoV-19 vaccines, but knowledge on individuals who received a single dose of Ad26.COV2.S is lacking.
Methods
We studied Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals (n = 55) who were either primed with Ad26.COV2.S only (n = 13) or were boosted with a homologous (Ad26.COV2.S, n = 28) or heterologous (BNT162b2, n = 14) second dose. We compared our findings with the results found in individuals vaccinated with a single (n = 16) or double (n = 44) dose of BNT162b2.
Findings
We observed that a strategy of heterologous vaccination enhanced the quantity and breadth of both Spike-specific humoral and cellular immunity in Ad26.COV2.S-vaccinated individuals. In contrast, the impact of the homologous boost was quantitatively minimal in Ad26.COV2.S-vaccinated individuals, and Spike-specific antibodies and T cells were narrowly focused to the S1 region.
Conclusions
Despite the small sample size of the study and the lack of well-defined correlates of protection against COVID-19, the immunological features detected support the utilization of a heterologous vaccine boost in individuals who received Ad26.COV2.S vaccination.
Funding
This study is partially supported by the Singapore Ministry of Health’s National Medical Research Council under its COVID-19 Research Fund (COVID19RF3-0060, COVID19RF-001, and COVID19RF-008), The Medical College St. Bartholomew’s Hospital Trustees – Pump Priming Fund for SMD COVID-19 Research.
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