scholarly journals Boosted Influenza-Specific T Cell Responses after H5N1 Pandemic Live Attenuated Influenza Virus Vaccination

2015 ◽  
Vol 6 ◽  
Author(s):  
YanChun Peng ◽  
Beibei Wang ◽  
Kawsar Talaat ◽  
Ruth Karron ◽  
Timothy J. Powell ◽  
...  
2008 ◽  
Vol 15 (8) ◽  
pp. 1171-1175 ◽  
Author(s):  
Tjitske de Boer ◽  
Jaap T. van Dissel ◽  
Taco W. J. Kuijpers ◽  
Guus F. Rimmelzwaan ◽  
Frank P. Kroon ◽  
...  

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.


2011 ◽  
Vol 31 (5) ◽  
pp. 900-912 ◽  
Author(s):  
Gillian M. Air ◽  
JingQi Feng ◽  
Tao Chen ◽  
Michelle L. Joachims ◽  
Judith A. James ◽  
...  

2007 ◽  
Vol 85 (3) ◽  
pp. 824-836 ◽  
Author(s):  
Josep Bassaganya-Riera ◽  
Amir J Guri ◽  
Alexis M Noble ◽  
Kathryn A Reynolds ◽  
Jennifer King ◽  
...  

2014 ◽  
Vol 45 (2) ◽  
pp. 624-635 ◽  
Author(s):  
Even Fossum ◽  
Gunnveig Grødeland ◽  
Dorothea Terhorst ◽  
Anders A. Tveita ◽  
Elisabeth Vikse ◽  
...  

2011 ◽  
Vol 11 (3) ◽  
pp. 613-618 ◽  
Author(s):  
A. P. Turner ◽  
V. O. Shaffer ◽  
K. Araki ◽  
C. Martens ◽  
P. L. Turner ◽  
...  

2012 ◽  
Vol 19 (11) ◽  
pp. 1792-1797 ◽  
Author(s):  
J. E. Ledgerwood ◽  
Z. Hu ◽  
I. J. Gordon ◽  
G. Yamshchikov ◽  
M. E. Enama ◽  
...  

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.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Yansheng Li ◽  
Mingkai Xu ◽  
Yongqiang Li ◽  
Wu Gu ◽  
Gulinare Halimu ◽  
...  

Influenza pandemics pose public health threats annually for lacking vaccine which provides cross-protection against novel and emerging influenza viruses. Combining conserved antigens that induce cross-protective antibody responses with epitopes that activate cross-protective T cell responses might be an attractive strategy for developing a universal vaccine. In this study, we constructed a recombinant protein named NMHC which consist of influenza viral conserved epitopes and a superantigen fragment. NMHC promoted the maturation of bone marrow-derived dendritic cells and induced CD4+ T cells to differentiate into Th1, Th2, and Th17 subtypes. Mice vaccinated with NMHC produced high levels of immunoglobulins that cross-bound to HA fragments from six influenza virus subtypes with high antibody titers. Anti-NMHC serum showed potent hemagglutinin inhibition effects to highly divergent group 1 (H1 subtype) and group 2 (H3 subtype) influenza virus strains. Furthermore, purified anti-NMHC antibodies bound to multiple HAs with high affinities. NMHC vaccination effectively protected mice from infection and lung damage when exposed to two subtypes of H1N1 influenza virus. Moreover, NMHC vaccination elicited CD4+ and CD8+ T cell responses that cleared the virus from infected tissues and prevented virus spread. In conclusion, this study provides proof of concept that NMHC vaccination triggers B and T cell immune responses against multiple influenza virus infections. Therefore, NMHC might be a candidate universal broad-spectrum vaccine for the prevention and treatment of multiple influenza viruses.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11021
Author(s):  
Pirom Noisumdaeng ◽  
Thaneeya Roytrakul ◽  
Jarunee Prasertsopon ◽  
Phisanu Pooruk ◽  
Hatairat Lerdsamran ◽  
...  

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.


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