Antibody and T cell responses induced in chickens immunized with avian influenza virus N1 and NP DNA vaccine with chicken IL-15 and IL-18

ABSTRACTAvian influenza virus causes outbreaks in domestic and wild birds around the world, and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized phase I clinical studies. Vaccine Research Center study 304 (VRC 304) was a double-blinded study with 45 subjects randomized to placebo, 1 mg of vaccine, or 4 mg of vaccine treatment groups (n= 15/group) by intramuscular (i.m.) Biojector injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (i.d.) injections of 0.5 mg by needle/syringe or by Biojector or 1 mg delivered as two 0.5-mg Biojector injections in the same deltoid or as 0.5 mg in each deltoid (n= 11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by hemagglutination inhibition (HAI) assay, enzyme-linked immunosorbent assay (ELISA), and neutralization assay, and the H5 T cell responses were assessed by enzyme-linked immunospot and intracellular cytokine staining assays. There were no vaccine-related serious adverse events, and the vaccine was well tolerated in all groups. At 1 mg, i.d. vaccination compared to i.m. vaccination induced a greater frequency and magnitude of response by ELISA, but there were no significant differences in the frequency or magnitude of response between the i.d. and i.m. routes in the HAI or neutralization assays. T cell responses were more common in subjects who received the 1- or 4-mg dose i.m. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The i.d. injection route did not offer a significant advantage over the i.m. route, and no difference was detected by delivery to one site versus splitting the dose between two sites for i.d. vaccine administration. The 4-mg dose (i.m) was further investigated in prime-boost regimens.

Download Full-text

T cell mediated immunity against influenza H5N1 nucleoprotein, matrix and hemagglutinin derived epitopes in H5N1 survivors and non-H5N1 subjects

PeerJ ◽

10.7717/peerj.11021 ◽

2021 ◽

Vol 9 ◽

pp. e11021

Author(s):

Pirom Noisumdaeng ◽

Thaneeya Roytrakul ◽

Jarunee Prasertsopon ◽

Phisanu Pooruk ◽

Hatairat Lerdsamran ◽

...

Keyword(s):

Flow Cytometry ◽

Influenza Virus ◽

T Cell ◽

Avian Influenza ◽

Influenza Vaccine ◽

Elispot Assay ◽

H5n1 Virus ◽

T Cell Responses ◽

Cell Responses ◽

Influenza H5n1

Background Protection against the influenza virus by a specific antibody is relatively strain specific; meanwhile broader immunity may be conferred by cell-mediated immune response to the conserved epitopes across influenza virus subtypes. A universal broad-spectrum influenza vaccine which confronts not only seasonal influenza virus, but also avian influenza H5N1 virus is promising. Methods This study determined the specific and cross-reactive T cell responses against the highly pathogenic avian influenza A (H5N1) virus in four survivors and 33 non-H5N1 subjects including 10 H3N2 patients and 23 healthy individuals. Ex vivo IFN-γ ELISpot assay using overlapping peptides spanning the entire nucleoprotein (NP), matrix (M) and hemagglutinin (HA) derived from A/Thailand/1(KAN-1)/2004 (H5N1) virus was employed in adjunct with flow cytometry for determining T cell functions. Microneutralization (microNT) assay was performed to determine the status of previous H5N1 virus infection. Results IFN-γ ELISpot assay demonstrated that survivors nos. 1 and 2 had markedly higher T cell responses against H5N1 NP, M and HA epitopes than survivors nos. 3 and 4; and the magnitude of T cell responses against NP were higher than that of M and HA. Durability of the immunoreactivity persisted for as long as four years after disease onset. Upon stimulation by NP in IFN-γ ELISpot assay, 60% of H3N2 patients and 39% of healthy subjects exhibited a cross-reactive T cell response. The higher frequency and magnitude of responses in H3N2 patients may be due to blood collection at the convalescent phase of the patients. In H5N1 survivors, the effector peptide-specific T cells generated from bulk culture PBMCs by in vitro stimulation displayed a polyfunction by simultaneously producing IFN-γ and TNF-α, together with upregulation of CD107a in recognition of the target cells pulsed with peptide or infected with rVac-NP virus as investigated by flow cytometry. Conclusions This study provides an insight into the better understanding on the homosubtypic and heterosubtypic T cell-mediated immune responses in H5N1 survivors and non-H5N1 subjects. NP is an immunodominant target of cross-recognition owing to its high conservancy. Therefore, the development of vaccine targeting the conserved NP may be a novel strategy for influenza vaccine design.

Download Full-text

Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates

PLoS ONE ◽

10.1371/journal.pone.0189780 ◽

2017 ◽

Vol 12 (12) ◽

pp. e0189780 ◽

Cited By ~ 14

Author(s):

Merika T. Koday ◽

Jolie A. Leonard ◽

Paul Munson ◽

Adriana Forero ◽

Michael Koday ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

Dna Vaccine ◽

Nonhuman Primates ◽

T Cell Responses ◽

Cell Responses

Download Full-text

Faculty Opinions recommendation of Characterization of T-cell responses in macaques immunized with a single dose of HIV DNA vaccine.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.2426978.2061078 ◽

2010 ◽

Author(s):

Willy Bogers ◽

Petra Mooij

Keyword(s):

Single Dose ◽

T Cell ◽

Dna Vaccine ◽

T Cell Responses ◽

Cell Responses ◽

Hiv Dna

Download Full-text

Individual Antibody and T Cell Responses to Vaccination and Infection with the 2009 Pandemic Swine-Origin H1N1 Influenza Virus

Journal of Clinical Immunology ◽

10.1007/s10875-011-9563-1 ◽

2011 ◽

Vol 31 (5) ◽

pp. 900-912 ◽

Cited By ~ 5

Author(s):

Gillian M. Air ◽

JingQi Feng ◽

Tao Chen ◽

Michelle L. Joachims ◽

Judith A. James ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

T Cell Responses ◽

H1n1 Influenza ◽

H1n1 Influenza Virus ◽

Cell Responses

Download Full-text

Arachidonic acid–and docosahexaenoic acid–enriched formulas modulate antigen-specific T cell responses to influenza virus in neonatal piglets

American Journal of Clinical Nutrition ◽

10.1093/ajcn/85.3.824 ◽

2007 ◽

Vol 85 (3) ◽

pp. 824-836 ◽

Cited By ~ 17

Author(s):

Josep Bassaganya-Riera ◽

Amir J Guri ◽

Alexis M Noble ◽

Kathryn A Reynolds ◽

Jennifer King ◽

...

Keyword(s):

Influenza Virus ◽

Arachidonic Acid ◽

T Cell ◽

Docosahexaenoic Acid ◽

T Cell Responses ◽

Neonatal Piglets ◽

Cell Responses

Download Full-text

Vaccine molecules targeting Xcr1 on cross-presenting DCs induce protective CD8+T-cell responses against influenza virus

European Journal of Immunology ◽

10.1002/eji.201445080 ◽

2014 ◽

Vol 45 (2) ◽

pp. 624-635 ◽

Cited By ~ 52

Author(s):

Even Fossum ◽

Gunnveig Grødeland ◽

Dorothea Terhorst ◽

Anders A. Tveita ◽

Elisabeth Vikse ◽

...

Keyword(s):

Influenza Virus ◽

T Cell ◽

T Cell Responses ◽

Cd8 T Cell ◽

Cell Responses

Download Full-text

Dendritic Cell Targeting Effectively Boosts T Cell Responses Elicited by an HIV Multiepitope DNA Vaccine

Frontiers in Immunology ◽

10.3389/fimmu.2017.00101 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 12

Author(s):

Juliana de Souza Apostólico ◽

Victória Alves Santos Lunardelli ◽

Marcio Massao Yamamoto ◽

Higo Fernando Santos Souza ◽

Edecio Cunha-Neto ◽

...

Keyword(s):

T Cell ◽

Dendritic Cell ◽

Dna Vaccine ◽

T Cell Responses ◽

Cell Targeting ◽

Cell Responses

Download Full-text

Infection of HLA-DR1 Transgenic Mice with a Human Isolate of Influenza A Virus (H1N1) Primes a Diverse CD4 T-Cell Repertoire That Includes CD4 T Cells with Heterosubtypic Cross-Reactivity to Avian (H5N1) Influenza Virus

Journal of Virology ◽

10.1128/jvi.00302-09 ◽

2009 ◽

Vol 83 (13) ◽

pp. 6566-6577 ◽

Cited By ~ 52

Author(s):

Katherine A. Richards ◽

Francisco A. Chaves ◽

Andrea J. Sant

Keyword(s):

T Cells ◽

Influenza Virus ◽

T Cell ◽

Avian Influenza ◽

Avian Influenza Virus ◽

Cd4 T Cells ◽

Cross Reactivity ◽

Cd4 T Cell ◽

Ns1 Protein ◽

Infected Cells

ABSTRACT The specificity of the CD4 T-cell immune response to influenza virus is influenced by the genetic complexity of the virus and periodic encounters with variant subtypes and strains. In order to understand what controls CD4 T-cell reactivity to influenza virus proteins and how the influenza virus-specific memory compartment is shaped over time, it is first necessary to understand the diversity of the primary CD4 T-cell response. In the study reported here, we have used an unbiased approach to evaluate the peptide specificity of CD4 T cells elicited after live influenza virus infection. We have focused on four viral proteins that have distinct intracellular distributions in infected cells, hemagglutinin (HA), neuraminidase (NA), nucleoprotein, and the NS1 protein, which is expressed in infected cells but excluded from virion particles. Our studies revealed an extensive diversity of influenza virus-specific CD4 T cells that includes T cells for each viral protein and for the unexpected immunogenicity of the NS1 protein. Due to the recent concern about pandemic avian influenza virus and because CD4 T cells specific for HA and NA may be particularly useful for promoting the production of neutralizing antibody to influenza virus, we have also evaluated the ability of HA- and NA-specific CD4 T cells elicited by a circulating H1N1 strain to cross-react with related sequences found in an avian H5N1 virus and find substantial cross-reactivity, suggesting that seasonal vaccines may help promote protection against avian influenza virus.

Download Full-text