Faculty Opinions recommendation of Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

ABSTRACT Both live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV) induce protective immunity against influenza. There is evidence that LAIV induces superior protection in children, whereas IIV may induce superior protection in adults. The immune mechanisms responsible for these differences have not been identified. We previously compared LAIV and IIV in young children of 6 to 36 months of age, and we demonstrated that while both induced similar hemagglutination inhibition (HAI) antibody responses, only LAIV induced significant increases in T cell responses. In the present study, 37 healthy adult subjects of 18 to 49 years of age were randomized to receive seasonal influenza vaccination with LAIV or IIV. Influenza virus-specific HAI, T cell, and secretory IgA (sIgA) responses were studied pre- and postvaccination. In contrast to the responses seen in young children, LAIV induced only minimal increases in serum HAI responses in adults, which were significantly lower than the responses induced by IIV. Both LAIV and IIV similarly induced only transient T cell responses to replication-competent whole virus in adults. In contrast, influenza virus-specific sIgA responses were induced more strongly by LAIV than by IIV. Our previous studies suggest that LAIV may be more protective than IIV in young children not previously exposed to influenza virus or influenza vaccines due to increased vaccine-induced T cell and/or sIgA responses. Our current work suggests that in adults with extensive and partially cross-reactive preexisting influenza immunity, LAIV boosting of sIgA responses to hemagglutinin (HA) and non-HA antigenic targets expressed by circulating influenza virus strains may be an important additional mechanism of vaccine-induced immunity.

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M2e-Based Influenza Vaccines with Nucleoprotein: A Review

Vaccines ◽

10.3390/vaccines9070739 ◽

2021 ◽

Vol 9 (7) ◽

pp. 739

Author(s):

Mei Peng Tan ◽

Wen Siang Tan ◽

Noorjahan Banu Mohamed Alitheen ◽

Wei Boon Yap

Keyword(s):

T Cell ◽

Influenza Vaccine ◽

Matrix Protein ◽

Severe Disease ◽

Chimeric Protein ◽

Influenza Vaccines ◽

Cell Responses ◽

Hospitalization Rates ◽

Humoral Responses ◽

Universal Influenza Vaccine

Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as Escherichia coli without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.

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The Dual-Antigen Ad5 COVID-19 Vaccine Delivered as an Intranasal Plus Subcutaneous Prime Elicits Th1 Dominant T-Cell and Humoral Responses in CD-1 Mice

10.1101/2021.03.22.436476 ◽

2021 ◽

Author(s):

Adrian Rice ◽

Mohit Verma ◽

Annie Shin ◽

Lise Zakin ◽

Peter Sieling ◽

...

Keyword(s):

T Cell ◽

Oral Delivery ◽

Surface Display ◽

T Cell Responses ◽

Human Adenovirus ◽

Cell Surface Display ◽

Mhc I ◽

Cell Responses ◽

Serotype 5 ◽

Humoral Responses

In response to the need for an efficacious, thermally-stable COVID-19 vaccine that can elicit both humoral and cell-mediated T-cell responses, we have developed a dual-antigen human adenovirus serotype 5 (hAd5) COVID-19 vaccine in formulations suitable for subcutaneous (SC), intranasal (IN), or oral delivery. The vaccine expresses both the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins using an hAd5 platform with E1, E2b, and E3 sequences deleted; hAd5(E1-, E2b-, E3-); that is effective even in the presence of hAd5 immunity. In the vaccine, S is modified (S-Fusion) for enhanced cell surface display to elicit humoral responses and N is modified with an Enhanced T-cell Stimulation Domain (N-ETSD) to direct N to the endosomal/lysosomal pathway to increase MHC I and II presentation. Initial studies using subcutaneous (SC) prime and SC boost vaccination of CD-1 mice demonstrated that the hAd5 S-Fusion + N-ETSD vaccine elicits T-helper cell 1 (Th1) dominant T-cell and humoral responses to both S and N. We then compared SC to IN prime vaccination with either an SC or IN boost post-SC prime and an IN boost after IN prime. These studies reveal that IN prime/IN boost is as effective at generating Th1 dominant humoral responses to both S and N as the other combinations, but that the SC prime with either an IN or SC boost elicits greater T cell responses. In a third study to assess the power of the two routes of delivery when used together, we used a combined SC plus IN prime with or without a boost and found the combined prime alone to be as effective as the combined prime with either an SC or IN boost in generating both humoral and T-cell responses. The findings here in CD-1 mice demonstrate that combined SC and IN prime-only delivery has the potential to provide broad immunity, including mucosal immunity, against SARS-CoV-2 and supports further testing of this delivery approach in additional animal models and clinical trials.

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Qualitative Differences in T cell responses to Live, Attenuated and Inactivated Influenza Vaccines

Journal of Clinical & Cellular Immunology ◽

10.4172/2155-9899.s4-002 ◽

2012 ◽

Vol 01 (S4) ◽

Cited By ~ 1

Author(s):

Maryna C. Eichelberger

Keyword(s):

T Cell ◽

T Cell Responses ◽

Influenza Vaccines ◽

Cell Responses

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Comparison of antibody and T-cell responses elicited by licensed inactivated- and live-attenuated influenza vaccines against H3N2 hemagglutinin

Human Immunology ◽

10.1016/j.humimm.2011.03.001 ◽

2011 ◽

Vol 72 (6) ◽

pp. 463-469 ◽

Cited By ~ 33

Author(s):

Saleem Basha ◽

Staci Hazenfeld ◽

Rebecca C. Brady ◽

Ramu A. Subbramanian

Keyword(s):

T Cell ◽

T Cell Responses ◽

Influenza Vaccines ◽

Cell Responses

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Cellular and humoral responses to SARS-CoV-2 vaccination in immunosuppressed patients

10.1101/2021.12.03.21267250 ◽

2021 ◽

Author(s):

Dinesh Mohanraj ◽

Samuel Baldwin ◽

Satbeer Singh ◽

Alun Gordon ◽

Alison Whitelegg

Keyword(s):

T Cell ◽

T Cell Responses ◽

Effector Memory ◽

Immunological Responses ◽

Vaccine Responses ◽

Cell Responses ◽

Immunosuppressed Patients ◽

Vaccine Immunogenicity ◽

Humoral Responses ◽

The Impact

ABSTRACTObjectiveSARS-CoV-2 vaccinations have demonstrated vaccine immunogenicity in healthy volunteers, however, efficacy in immunosuppressed patients is less well characterised. Subsequently, there is an urgent need to address the impact of immunosuppression on vaccine immunogenicity.MethodsSerological, T-cell ELISpot, cytokines and immunophenotyping investigations were used to assess vaccine responses (either BNT162b2 mRNA or ChAdOx1 nCoV-19) in double-vaccinated patients receiving immunosuppression for renal transplants or haematological malignancies (n=13). Immunological responses in immunosuppressed patients (VACC-IS) were compared to immunocompetent vaccinated (VACC-IC, n=12), unvaccinated (UNVACC, n=11) and infection-naïve unvaccinated (HC, n=3) cohorts. All participants, except HC, had prior COVID-19 infection.ResultsT-cell responses were identical between VACC-IS and VACC-IC (92%) to spike-peptide (S) stimulation. UNVACC had the highest T-cell non-responders (n=3), whereas VACC-IC and VACC-IS both had one T-cell non-responder. No significant differences in humoral responses were observed between VACC-IC and VACC-IS, with 92% (12/13) of VACC-IS patients demonstrating seropositivity. One VACC-IS failed to seroconvert, however had detectable T-cell responses. All VACC-IC participants were seropositive for anti-spike antibodies. Furthermore, both VACC-IS and VACC-IC participants elicited strong Th1 cytokine response with immunodominance towards S-peptide. Differences in T-cell immunophenotyping were seen between VACC-IS and VACC-IC, with lower CD8+ activation and T-effector memory phenotype observed in VACC-IS.ConclusionSARS-CoV-2 vaccines are immunogenic in patients receiving immunosuppressive therapy, with responses comparable to vaccinated immunocompetent participants. Lower humoral responses were seen in patients treated with B-cell depleting therapeutics, but with preserved T-cell responses. We suggest further work to correlate both protective immunity and longevity of these responses in both healthy and immunosuppressed patients.

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Exploring T Cell Reactivity to Gliadin in Young Children with Newly Diagnosed Celiac Disease

Autoimmune Diseases ◽

10.1155/2014/927190 ◽

2014 ◽

Vol 2014 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Edwin Liu ◽

Kristen McDaniel ◽

Stephanie Case ◽

Liping Yu ◽

Bernd Gerhartz ◽

...

Keyword(s):

T Cells ◽

Celiac Disease ◽

T Cell ◽

Young Children ◽

Peripheral Blood ◽

T Cell Responses ◽

Cd4 T Cell ◽

Newly Diagnosed ◽

Cell Responses ◽

Gliadin Peptides

Class II major histocompatibility molecules confer disease risk in Celiac disease (CD) by presenting gliadin peptides to CD4 T cells in the small intestine. Deamidation of gliadin peptides by tissue transglutaminase creates immunogenic peptides presented by HLA-DQ2 and DQ8 molecules to activate proinflammatory CD4 T cells. Detecting gliadin specific T cell responses from the peripheral blood has been challenging due to low circulating frequencies and heterogeneity in response to gliadin epitopes. We investigated the peripheral T cell responses to alpha and gamma gliadin epitopes in young children with newly diagnosed and untreated CD. Using peptide/MHC recombinant protein constructs, we are able to robustly stimulate CD4 T cell clones previously derived from intestinal biopsies of CD patients. These recombinant proteins and a panel ofα- andγ-gliadin peptides were used to assess T cell responses from the peripheral blood. Proliferation assays using peripheral blood mononuclear cells revealed more CD4 T cell responses toα-gliadin thanγ-gliadin peptides with a single deamidatedα-gliadin peptide able to identify 60% of CD children. We conclude that it is possible to detect T cell responses without a gluten challenge or in vitro stimulus other than antigen, when measuring proliferative responses.

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