Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants

Kingstad-Bakke, Brock; Lee, Woojong; Chandrasekar, S; Gasper, David J.; Salas-Quinchucua, Cristhian; Cleven, Thomas; Sullivan, Jeremy A.; Talaat, Adel M.; Osorio, Jorge E.; Suresh, M.

doi:10.1073/pnas.2118312119

Cited by 90 publications

(83 citation statements)

References 44 publications

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“…However, this is yet to be tested directly and the role of lung T-cells and systemic nAbs in mediating protection against SARS-CoV-2 in isolation needs to be further validated. Recent studies have shown the ability of vaccine-induced mucosal T-cells in mediating protection against SARS-CoV-2 variants even in the absence of complementing nAbs, similar to our studies, underscoring their importance for SARS-CoV-2 control [48]. In line with our clinical and viral load data, reduced viral pneumonia in the lungs of pQAC-CoV IM-vaccinated mice were observed.…”

Section: Discussionsupporting

confidence: 92%

Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2

Chandrasekar

Phanse

Riel

et al. 2022

Viruses

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Antibody measurements are primarily used to evaluate experimental and approved COVID-19 vaccines, which is unilateral considering our immune responses’ complex nature. Previously, we showed that nanoparticle plasmid DNA adjuvant system, QAC, and MVA based vaccines were immunogenic against SARS-CoV-2. Here, we report on the protective efficacy of systemic humoral and mucosal cell-mediated immune responses in transgenic mice models against SARS-CoV-2 following nanoparticle immunization. Parenteral, intramuscular administration of QAC-based plasmid DNA vaccine-encoding SARS-CoV-2 S and N led to the induction of significant serum neutralizing humoral responses, which reduced viral burden in the lungs and prevented viral dissemination to the brain. In contrast, the mucosal, intranasal administration of a heterologous vaccine elicited significant mucosal cell-mediated immune responses in the lungs that limited lung viral replication. The presented results demonstrate that serum neutralizing humoral and local lung T-cell immune responses are critical for the control of SARS-CoV-2 replication.

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Section: Discussionsupporting

confidence: 92%

Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2

Chandrasekar

Phanse

Riel

et al. 2022

Viruses

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“…Interestingly, although the recombinant virus was not effective in significant reduction of viral loads in the lungs of challenged Syrian hamsters, the animals were protected against lung immunopathology. These data are in line with other studies which found that virus-neutralizing antibodies are more effective in virus control than the T cells, but CD4 and CD8 T cells can effectively protect hamsters against antibody-resistant SARS-CoV-2 variants, without inducing lung immunopathology [75].…”

Section: Discussionsupporting

confidence: 91%

Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector

et al. 2022

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The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP366 influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2.

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“…Antibody responses are crucial to mediate neutralization and antibody-dependent cellular functions against viruses and most important for clearance of extracellular pathogens. While strong humoral responses are indicators of protection from infection and transmission, T cells mediate or “help” such antibody responses (CD4 T helper cells) as well as protect from severe disease by clearing all infected cells (CD8 cytotoxic T cells) ( 68 , 69 ).…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, further decline of the cross-reactivity of T cell responses to other VoCs could translate into lower protection from severe disease over time. It is important to continue to monitor the duration and cross-reactivity of T cell responses induced by different vaccine platforms, to determine if a T-cell inducing vaccination/booster would be beneficial to make both cellular and humoral responses long-lasting and eliminate the need for regular vaccination ( 68 ). In particular, combination of different vaccination strategies may elicit strong tissue-resident T cell responses in the mucosa, as well as mucosal antibodies, that could confer long-lasting protection from immune-evasive VoCs ( 73 ), also highlighting the importance of mucosal responses to protect from respiratory viral pathogens ( 74 ).…”

Section: Discussionmentioning

confidence: 99%

Post-vaccination T cell immunity to omicron

et al. 2022

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In late 2021, the omicron variant of SARS Coronavirus 2 (SARS-CoV-2) emerged and replaced the previously dominant delta strain. Effectiveness of COVID-19 vaccines against omicron has been challenging to estimate in clinical studies or is not available for all vaccines or populations of interest. T cell function can be predictive of vaccine longevity and effectiveness against disease, likely in a more robust way than antibody neutralization. In this mini review, we summarize the evidence on T cell immunity against omicron including effects of boosters, homologous versus heterologous regimens, hybrid immunity, memory responses and vaccine product. Overall, T cell reactivity in post-vaccine specimens is largely preserved against omicron, indicating that vaccines utilizing the parental antigen continue to be protective against disease caused by the omicron variant.

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Vaccine-induced systemic and mucosal T cell immunity to SARS-CoV-2 viral variants

Cited by 90 publications

References 44 publications

Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2

Systemic Neutralizing Antibodies and Local Immune Responses Are Critical for the Control of SARS-CoV-2

Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector

Post-vaccination T cell immunity to omicron

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