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Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines.

ABSTRACT: Despite the successes of current coronavirus disease 2019 (COVID-19) vaccines, waning immunity, the emergence of variants of concern, and breakthrough infections among vaccinees have begun to highlight opportunities to improve vaccine platforms. Real-world vaccine efficacy studies have highlighted the reduced risk of breakthrough infections and diseases among individuals infected and vaccinated, referred to as hybrid immunity. Thus, we sought to define whether hybrid immunity shapes the humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following Pfizer/BNT162b2, Moderna mRNA-1273, ChadOx1/AZD1222, and Ad26.COV2.S vaccination. Each vaccine exhibits a unique functional humoral profile in vaccination only or hybrid immunity. However, hybrid immunity shows a unique augmentation of S2-domain-specific functional immunity that was poorly induced for the vaccination only. These data highlight the importance of natural infection in breaking the immunodominance away from the evolutionarily unstable S1 domain and potentially affording enhanced cross-variant protection by targeting the more highly conserved S2 domain of SARS-CoV-2.

SUBMITTER: Kaplonek P

PROVIDER: S-EPMC10126214 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines.

Kaplonek Paulina P Deng Yixiang Y Shih-Lu Lee Jessica J Zar Heather J HJ Zavadska Dace D Johnson Marina M Lauffenburger Douglas A DA Goldblatt David D Alter Galit G

Cell reports. Medicine 20230425 5

Despite the successes of current coronavirus disease 2019 (COVID-19) vaccines, waning immunity, the emergence of variants of concern, and breakthrough infections among vaccinees have begun to highlight opportunities to improve vaccine platforms. Real-world vaccine efficacy studies have highlighted the reduced risk of breakthrough infections and diseases among individuals infected and vaccinated, referred to as hybrid immunity. Thus, we sought to define whether hybrid immunity shapes the humoral ...[more]

PMID: 37182520

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Project description:BackgroundComparing humoral responses in SARS-CoV-2 vaccinees, those with SARS-CoV-2 infection, or combinations of vaccine/infection ('hybrid immunity'), may clarify predictors of vaccine immunogenicity.MethodsWe studied 2660 U.S. Military Health System beneficiaries with a history of SARS-CoV-2 infection-alone (n = 705), vaccination-alone (n = 932), vaccine-after-infection (n = 869), and vaccine-breakthrough-infection (n = 154). Peak anti-spike-IgG responses through 183 days were compared, with adjustment for vaccine product, demography, and comorbidities. We excluded those with evidence of clinical or sub-clinical SARS-CoV-2 reinfection from all groups.ResultsMultivariable regression results indicated vaccine-after-infection anti-spike-IgG responses were higher than infection-alone (p < 0.01), regardless of prior infection severity. An increased time between infection and vaccination was associated with a greater post-vaccination IgG response (p < 0.01). Vaccination-alone elicited a greater IgG response, but more rapid waning of IgG (p < 0.01), compared to infection-alone (p < 0.01). BNT162b2 and mRNA-1273 vaccine-receipt was associated with greater IgG responses compared to JNJ-78436735 (p < 0.01), regardless of infection history. Those with vaccine-after-infection or vaccine-breakthrough-infection had a more durable anti-spike-IgG response compared to infection-alone (p < 0.01).ConclusionsVaccine-receipt elicited higher anti-spike-IgG responses than infection-alone, although IgG levels waned faster in those vaccinated (compared to infection-alone). Vaccine-after-infection elicits a greater humoral response compared to vaccine or infection alone; and the timing, but not disease severity, of prior infection predicted these post-vaccination IgG responses. While differences between groups were small in magnitude, these results offer insights into vaccine immunogenicity variations that may help inform vaccination timing strategies.

Project description:BackgroundLongitudinal humoral SARS-CoV-2 (severe acute respiratory syndrome coronavirus type 2) immunity for up to 15 months due to vaccination, the efficacy of vaccination strategies (homologous, vector-vector versus heterologous, vector-mRNA), the influence of vaccination side effects, and the infection rate in German healthcare workers need to be investigated.MethodsIn this study, 103 individuals vaccinated against SARS-CoV-2 were enrolled to examine their anti-SARS-CoV-2 anti-N- and anti-RBD/S1-Ig levels. A total of 415 blood samples in lithium heparin tubes were prospectively obtained, and a structured survey regarding medical history, type of vaccine, and vaccination reactions was conducted.ResultsAll participants demonstrated a humoral immune response, among whom no values decreased below the positivity cutoff. Five to six months after the third vaccination, three participants showed anti-RBD/S1 antibodies of less than 1000 U/mL. We observed higher levels for heterologous mRNA-/vector-based combinations compared to pure vector-based vaccination after the second vaccination, which is harmonized after a third vaccination with the mRNA-vaccine only in both cohorts. The incidence of vaccine breakthrough in a highly exposed cohort was 60.3%.ConclusionSustained long-term humoral immunity was observed, indicating the superiority of a heterologous mRNA-/vector-based combination compared to pure vector-based vaccination. There was longevity of anti-RBD/S1 antibodies of at least 4 and up to 7 months without external stimulus. Regarding vaccination reactogenity, the occurrence of local symptoms as pain at the injection site was increased after the first mRNA application compared to the vector-vector cohort with a general decrease in adverse events at later vaccination time points. Overall, a correlation between the humoral vaccination response and vaccination side effects was not observed. Despite the high prevalence of vaccine breakthroughs, these only occurred in the later course of the study when more infectious variants, which are, however, associated with milder courses, were present. These results provide insights into vaccine-related serologic responses, and the study should be expanded using additional vaccine doses and novel variants in the future.

Project description:We investigated how differences in age, sex, or vaccine type can affect humoral and cellular immune responses after vaccination with vector (ChAdOx1 nCoV-19), mix-and-match (first, ChAdOx1 nCoV-19, and second, BNT162b2), or mRNA (BNT162b2 or mRNA-1273) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Venous blood was collected from 573 subjects (vector, 396; mix-and-match, 96; and mRNA, 81) before the first vaccination (T0), 7 to 8 weeks (vector) or 3 to 4 weeks (mRNA) after the first vaccination (T1), and 3 to 4 weeks after the second vaccination (T2). The humoral and cellular immune responses were evaluated using Elecsys anti-SARS-CoV-2 (Roche), Alinity SARS-CoV-2 IgG II Quant (Abbott), cPass SARS-CoV-2 neutralization antibody detection (GenScript), and QuantiFERON SARS-CoV-2 (Qiagen) kits. At T1, the levels of the receptor-binding domain antibodies (RBD Ab) and neutralizing antibodies (NAb) decreased with aging, but interferon gamma release (IGR) levels increased. The RBD Ab, NAb, and IGR levels were higher in females than in males at T1 and T2. The NAb levels were higher in the mix-and-match and mRNA vaccine groups than in the vector vaccine group at T2. The RBD Ab and IGR levels were higher in the mRNA vaccine group than in the vector or mix-and-match vaccine groups at T2. The optimal cutoffs for RBD Ab and NAb, which were used to determine the presence of T cell responses, were 5.7 binding antibody units per milliliter (BAU mL-1) and 12.0 IU mL-1, respectively. Age, sex, and vaccine type affected the humoral and cellular immune responses, and T cell responses could be estimated from RBD Ab and NAb levels. IMPORTANCE There have been few studies that comprehensively evaluated factors affecting immune responses and the correlation between humoral and cellular immune responses after vector, mix-and-match, and mRNA vaccines against SARS-CoV-2. Therefore, we analyzed the effects of age, sex, and the different vaccine regimens on the immune responses to vaccination against SARS-CoV-2. The correlation between humoral and cellular immune responses and the cutoffs were derived for RBD antibodies and neutralizing antibodies to predict the presence of the cellular immune responses. In this comprehensive study, we demonstrated that there were differences in the immune responses induced after vaccination depending on the age and sex of an individual. Among the three vaccine regimens, the mix-and-match and mRNA vaccines induced the most robust immune responses. Finally, the proposed optimal cutoffs for RBD and neutralizing antibodies may be useful for predicting cellular immune responses when assays for cellular immune responses are not available.

Dataset Information

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines.

Publications

Hybrid immunity expands the functional humoral footprint of both mRNA and vector-based SARS-CoV-2 vaccines.

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