In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

Heinen, Natalie; Marheinecke, Corinna; Bessen, Clara; Blázquez-Navarro, Arturo; Roch, Toralf; Stervbo, Ulrik; Anft, Moritz; Plaza-Sirvent, Carlos; Buße, Sandra; Klöhn, Mara; Schrader, Jil Alexandra; Blanco, Elena Vidal; Urlaub, Doris; Watzl, Carsten; Hoffmann, Markus; Pöhlmann, Stefan; Tenbusch, Matthias; Steinmann, Eike; Todt, Daniel; Hagenbeck, Carsten; Zimmer, Gert; Schmidt, Wolfgang E.; Babel, Nina; Schmitz, Ingo; Pfänder, Stephanie

doi:10.3389/fimmu.2022.1062210

Cited by 5 publications

(2 citation statements)

References 79 publications

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“…The clinical association of T cells with viral load and disease severity in SARS-CoV-2 infection is not yet characterized. Still, systemic inflammation, virus-specific T-cell responses, and severe pneumonia have contributed to tissue damage in other respiratory infections (41). The absolute number of CD + 4 and CD + 8 T cells was decreased in COVID-19 patients, and the decline in T lymphocyte counts was correlated with disease severity.…”

Section: Adaptive Immunitymentioning

confidence: 99%

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

Gupta,

Rao

2023

Preprint

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The newly emerged variants of SARS-CoV-2 created a potential threat among societies and highlighted one of the significant concerns in facing the pandemic. SARS-CoV-2 variants harboring mutations in the structural protein, especially in the RBD domain of spike protein, have raised concern about potential immune escape. The spike protein of SARS-CoV-2 play a vital role in infection and is an important target for neutralizing antibodies. The mutations that occur in the structural proteins, especially in the spike protein, lead to changes in the virus attributes of transmissibility, an increase in disease severity, a notable reduction in neutralizing antibodies generated, and thus a decreased response to vaccines and therapy. The immune response against SARS-CoV-2 has been reported mainly through innate immune responses rather than adaptive immune responses. SARS-CoV-2 invades the host's innate immunity, possibly through inducing cytokine storm, impairing type I IFN responses, and suppressing antigens presentation to T cells. Therefore, the adaptive immune response is required to combat SARS-CoV-2 infection. The SARS-CoV-2 infections activated both arms of adaptive immunity; humoral and cell-mediated immunity. The observed multiple mutations in the RBD domain of the spike protein compromised the adaptive immune response and showed immune escape because it increases the affinity of spike protein binding with the ACE-2 receptor of host cells and increases resistance to neutralizing antibodies. Cytotoxic T-cell responses are crucial in controlling SARS-CoV-2 infections from the infected tissues and clearing them from circulation. CD8+cytotoxic T cells identify and directly kill the infected cells by releasing soluble mediators perforin and granzymes. The functional exhaustion of cytotoxic T cells may increase the severity of the disease. The expression of activation markers of T cells could indicate hyperactivation or functional exhaustion; the exact implication is not yet understood in SARS-CoV-2 infections. These mutations at critical residues influence the antigenic profile of SARS-CoV-2, which may evade the immune responses and thus reduce the immunogenicity and efficacy of vaccines. Therefore, the spike protein may be recognized as a primary target for vaccines and drugs. This review article summarizes the impact of mutations in the spike protein of SARS-CoV-2, especially mutations of RBD, on immunogenicity, immune escape, and vaccine-induced immunity, which could potentially contribute to future studies focusing on vaccine design and immunotherapy.

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Section: Adaptive Immunitymentioning

confidence: 99%

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

Gupta,

Rao

2023

Preprint

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“…T cell responses were conspicuously comparable between the various vaccination regimen using AZD1222 and/or BNT162b2 ( 10 , 13 , 15 ). After three vaccine doses and 12 months after primary immunization, differences in antibody quantity resulting from the primary vaccination regimen were hardly discernible; however, primary vaccination including BNT162b2 impacted positively on the recognition of the omicron variant of concern ( 15 – 18 ). We here set out to analyze the spike-specific immune responses at 18 months after primary immunization.…”

Section: Introductionmentioning

confidence: 99%

The varying extent of humoral and cellular immune responses to either vector- or RNA-based SARS-CoV-2 vaccines persists for at least 18 months and is independent of infection

Mai,

Bergmann,

Reisinger

et al. 2024

J Virol

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The corona virus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) spurred a worldwide race for the development of an efficient vaccine. Various strategies were pursued; however, the first vaccines to be licensed presented the SARS-CoV-2 spike protein either in the context of a non-replicating adenoviral vector or as an mRNA construct. While short-term efficacies have extensively been characterized, the duration of protection, the need for repeated boosting, and reasonable vaccination intervals have yet to be defined. We here describe the adaptive immune response resulting from homologous and heterologous vaccination regimen at 18 months after primary vaccination. To that extent, we monitored 176 healthcare workers, the majority of whom had recovered from previous SARS-CoV-2 infection. In summary, we find that differences depending on primary immunization continue to exist 18 months after the first vaccination and these findings hold true irrespective of previous infection with the virus. Homologous primary immunization with BNT162b2 was repeatedly shown to produce higher antibody levels and slower antibody decline, leading to more effective in vitro neutralization capacities. Likewise, cellular responses resulting from in vitro re-stimulation were more pronounced after primary immunization involving BNT162b2. In contrast, IL-2 producing memory T helper and cytotoxic T cells appeared independent from the primary vaccination regimen. Despite these differences, comparable infection rates among all vaccination groups suggest comparable real-life protection. IMPORTANCE Vaccination against the severe acute respiratory syndrome corona-virus 2 (SARS-CoV-2) was shown to avert severe courses of corona virus disease 2019 (COVID-19) and to mitigate spreading of the virus. However, the duration of protection and need for repeated boosting have yet to be defined. Monitoring and comparing the immune responses resulting from various vaccine strategies are therefore important to fill knowledge gaps and prepare for future pandemics.

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Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents

Rothoeft,

Maier,

Talarico

et al. 2024

Infection

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Purpose In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response. Methods 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3–26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA). Results All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity. Conclusion Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity.

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In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

Cited by 5 publications

References 79 publications

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

Emerging SARS-CoV-2 Variants and Their Impact on Immune Evasion and Vaccine-Induced Immunity

The varying extent of humoral and cellular immune responses to either vector- or RNA-based SARS-CoV-2 vaccines persists for at least 18 months and is independent of infection

Natural and hybrid immunity after SARS-CoV-2 infection in children and adolescents

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