Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses

ABSTRACTAgainst a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.IMPORTANCEWe revealed preexisting but biased T-cell reactivity of pH1N1 influenza virus to human-infecting AIVs, which provided distinct protections. The cross-reactive T-cell recognition had a regular pattern that depended on the T-cell epitope matrix revealed via bioinformatics analysis. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

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Immunogenicity of a Recombinant Influenza Virus Bearing Both the CD4+ and CD8+ T Cell Epitopes of Ovalbumin

Journal of Biomedicine and Biotechnology ◽

10.1155/2011/497364 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Bruno Garulli ◽

Giuseppina Di Mario ◽

Ester Sciaraffia ◽

Yoshihiro Kawaoka ◽

Maria R. Castrucci

Keyword(s):

T Cells ◽

Influenza Virus ◽

T Cell ◽

Cell Epitope ◽

Cd8 T Cell ◽

Influenza Viruses ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Additional Tool

Recombinant influenza viruses that bear the single immunodominant CD8+ T cell epitopeOVA257−264or the CD4+ T cell epitopeOVA323−339of the model antigen ovalbumin (OVA) have been useful tools in immunology. Here, we generated a recombinant influenza virus,WSN-OVAI/II, that bears both OVA-specific CD8+ and CD4+ epitopes on its hemagglutinin molecule. Live and heat-inactivatedWSN-OVAI/IIviruses were efficiently presented by dendritic cellsin vitroto OT-I TCR transgenic CD8+ T cells and OT-II TCR transgenic CD4+ T cells.In vivo,WSN-OVAI/IIvirus was attenuated in virulence, highly immunogenic, and protected mice from B16-OVA tumor challenge in a prophylactic model of vaccination. Thus,WSN-OVAI/IIvirus represents an additional tool, along with OVA TCR transgenic mice, for further studies on T cell responses and may be of value in vaccine design.

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CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus

10.1101/2020.05.20.107292 ◽

2020 ◽

Cited By ~ 3

Author(s):

Chloe H. Lee ◽

Mariana Pereira Pinho ◽

Paul Buckley ◽

Isaac Woodhouse ◽

Graham Ogg ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

Vaccine Development ◽

Sequence Similarity ◽

Cd8 T Cell ◽

Cross Reactivity ◽

T Cell Response ◽

Influenza Viruses ◽

Immune Memory ◽

T Cell Epitopes

AbstractWhile individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.

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Influenza Virus Vaccination Induces Interleukin-12/23 Receptor β1 (IL-12/23Rβ1)-Independent Production of Gamma Interferon (IFN-γ) and Humoral Immunity in Patients with Genetic Deficiencies in IL-12/23Rβ1 or IFN-γ Receptor I

Clinical and Vaccine Immunology ◽

10.1128/cvi.00090-08 ◽

2008 ◽

Vol 15 (8) ◽

pp. 1171-1175 ◽

Cited By ~ 8

Author(s):

Tjitske de Boer ◽

Jaap T. van Dissel ◽

Taco W. J. Kuijpers ◽

Guus F. Rimmelzwaan ◽

Frank P. Kroon ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

Seasonal Influenza ◽

Gamma Interferon ◽

Interleukin 12 ◽

Virus Vaccination ◽

Cell Responses ◽

Antibody Titers ◽

Ifn Γ ◽

Striking Contrast

ABSTRACT To investigate whether protective immune responses can be induced in the absence of normal interleukin-12/23/gamma interferon (IL-12/23/IFN-γ) axis signaling, we vaccinated with the seasonal influenza virus subunit vaccine two patients with complete IL-12/23 receptor β1 (IL-12/23Rβ1) deficiencies, two patients with partial IFN-γ receptor I (pIFN-γRI) deficiencies, and five healthy controls. Blood samples were analyzed before, 7 days after, and 28 days after vaccination. In most cases, antibody titers reached protective levels. Moreover, although T-cell responses in patients were lower than those observed in controls, significant influenza virus-specific T-cell proliferation, IFN-γ production, and numbers of IFN-γ-producing cells were found in all patients 7 days after the vaccination. Interestingly, influenza virus-specific IFN-γ responses were IL-12/23 independent, in striking contrast to mycobacterium-induced IFN-γ production. In conclusion, influenza virus vaccination induces IL-12/23-independent IFN-γ production by T cells and can result in sufficient humoral protection in both IL-12/23Rβ1- and pIFN-γRI-deficient individuals.

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Cross-Priming of T Cell Responses by Synthetic Microspheres Carrying a CD8+ T Cell Epitope Requires an Adjuvant Signal

The Journal of Immunology ◽

10.4049/jimmunol.174.6.3432 ◽

2005 ◽

Vol 174 (6) ◽

pp. 3432-3439 ◽

Cited By ~ 13

Author(s):

Florence Boisgérault ◽

Paloma Rueda ◽

Cheng Ming Sun ◽

Sandra Hervas-Stubbs ◽

Marie Rojas ◽

...

Keyword(s):

T Cell ◽

Cell Epitope ◽

T Cell Responses ◽

Cd8 T Cell ◽

T Cell Epitope ◽

Cell Responses

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Generation of Live Attenuated Influenza Virus by Using Codon Usage Bias

Journal of Virology ◽

10.1128/jvi.01443-15 ◽

2015 ◽

Vol 89 (21) ◽

pp. 10762-10773 ◽

Cited By ~ 20

Author(s):

Rebecca L. Y. Fan ◽

Sophie A. Valkenburg ◽

Chloe K. S. Wong ◽

Olive T. W. Li ◽

John M. Nicholls ◽

...

Keyword(s):

Influenza Virus ◽

Avian Influenza ◽

Codon Usage ◽

Codon Bias ◽

Seasonal Influenza ◽

Viral Proteins ◽

Influenza Viruses ◽

Donor Strain ◽

Avian Influenza Viruses ◽

Attenuated Viruses

ABSTRACTSeasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses with vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells but not in eggs by converting its codon usage so that it is similar to that observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral, and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus, our approach is a successful strategy to generate attenuated viruses for future application as vaccines.IMPORTANCEVaccination has been one of the best protective measures in combating influenza virus infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of the codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern over reverse mutations. The potential use of this kind of codon bias mutant as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.

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Induction of Polyomavirus-Specific CD8+T Lymphocytes by Distinct Dendritic Cell Subpopulations

Journal of Virology ◽

10.1128/jvi.75.1.544-547.2001 ◽

2001 ◽

Vol 75 (1) ◽

pp. 544-547 ◽

Cited By ~ 9

Author(s):

Donald R. Drake ◽

Mandy L. Shawver ◽

Annette Hadley ◽

Eric Butz ◽

Charles Maliszewski ◽

...

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Cell Epitope ◽

T Cell Responses ◽

T Cell Epitope ◽

Cell Responses ◽

Cd8 T Lymphocytes ◽

Cell Subpopulations ◽

Antigen Presenting

ABSTRACT Dendritic cells are pivotal antigen-presenting cells for generating adaptive T-cell responses. Here, we show that dendritic cells belonging to either the myeloid-related or lymphoid-related subset are permissive for infection by mouse polyomavirus and, when loaded with a peptide corresponding to the immunodominant anti-polyomavirus CD8+T-cell epitope or infected by polyomavirus, are each capable of driving expansion of primary polyomavirus-specific CD8+ T-cell responses in vivo.

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Immunogenicity and Cross-Reactivity of Rhesus Adenoviral Vectors

Journal of Virology ◽

10.1128/jvi.00159-18 ◽

2018 ◽

Vol 92 (11) ◽

Cited By ~ 2

Author(s):

M. Justin Iampietro ◽

Rafael A. Larocca ◽

Nicholas M. Provine ◽

Peter Abbink ◽

Zi Han Kang ◽

...

Keyword(s):

T Cell ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

T Cell Responses ◽

Adenoviral Vectors ◽

Cross Reactivity ◽

Human Populations ◽

Humoral Immune ◽

Cell Responses ◽

The Impact

ABSTRACT Adenovirus (Ad) vectors are being investigated as vaccine candidates, but baseline antivector immunity exists in human populations to both human Ad (HuAd) and chimpanzee Ad (ChAd) vectors. In this study, we investigated the immunogenicity and cross-reactivity of a panel of recently described rhesus adenoviral (RhAd) vectors. RhAd vectors elicited T cells with low exhaustion markers and robust anamnestic potential. Moreover, RhAd vector immunogenicity was unaffected by high levels of preexisting anti-HuAd immunity. Both HuAd/RhAd and RhAd/RhAd prime-boost vaccine regimens were highly immunogenic, despite a degree of cross-reactive neutralizing antibodies (NAbs) between phylogenetically related RhAd vectors. We observed extensive vector-specific cross-reactive CD4 T cell responses and more limited CD8 T cell responses between RhAd and HuAd vectors, but the impact of vector-specific cellular responses was far less than that of vector-specific NAbs. These data suggest the potential utility of RhAd vectors and define novel heterologous prime-boost strategies for vaccine development. IMPORTANCE To date, most adenoviral vectors developed for vaccination have been HuAds from species B, C, D, and E, and human populations display moderate to high levels of preexisting immunity. There is a clinical need for new adenoviral vectors that are not hindered by preexisting immunity. Moreover, the development of RhAd vector vaccines expands our ability to vaccinate against multiple pathogens in a population that may have received other HuAd or ChAd vectors. We evaluated the immunogenicity and cross-reactivity of RhAd vectors, which belong to the poorly described adenovirus species G. These vectors induced robust cellular and humoral immune responses and were not hampered by preexisting anti-HuAd vector immunity. Such properties make RhAd vectors attractive as potential vaccine vectors.

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Perforin and Fas Cytolytic Pathways Coordinately Shape the Selection and Diversity of CD8+-T-Cell Escape Variants of Influenza Virus

Journal of Virology ◽

10.1128/jvi.79.13.8545-8559.2005 ◽

2005 ◽

Vol 79 (13) ◽

pp. 8545-8559 ◽

Cited By ~ 18

Author(s):

Graeme E. Price ◽

Lei Huang ◽

Rong Ou ◽

Menghua Zhang ◽

Demetrius Moskophidis

Keyword(s):

Influenza Virus ◽

T Cell ◽

Vaccine Development ◽

Influenza Virus Infection ◽

Influenza Viruses ◽

Viral Escape ◽

Viral Control ◽

Ctl Escape ◽

Selection Of

ABSTRACT Antigenic variation is a viral strategy exploited to promote survival in the face of the host immune response and represents a major challenge for efficient vaccine development. Influenza viruses are pathogens with high transmissibility and mutation rates, enabling viral escape from immunity induced by prior infection or vaccination. Intense selection from neutralizing antibody drives antigenic changes in the surface glycoproteins, resulting in emergence of new strains able to reinfect hosts immune to previously circulating viruses. CD8+ cytotoxic T cells (CTLs) also provide protective immunity from influenza virus infection and may contribute to the antigenic evolution of influenza viruses. Utilizing mice transgenic for an influenza virus NP366-374 peptide-specific T-cell receptor, we demonstrated that the respiratory tract is a suitable site for generation of escape variants of influenza virus selected by CTL in vivo. In this report the contributions of the perforin and Fas pathways utilized by influenza virus-specific CTLs in viral clearance and selection of CTL escape variants have been evaluated. While transgenic CTLs deficient in either perforin- or Fas-mediated pathways are efficient in initial pulmonary viral control, variant virus emergence was observed in all the mice studied, although the spectrum of viral CTL escape variants selected varied profoundly. Thus, a less-restricted repertoire of escape variants was observed in mice with an intact perforin cytotoxic pathway compared with a limited variant diversity in perforin pathway-deficient mice, although maximal variant diversity was observed in mice having both Fas and perforin pathways intact. We conclude that selection of viral CTL escape variants reflects coordinate action between the tightly controlled perforin/granzyme pathway and the more promiscuous Fas/FasL pathway.

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