Identification of H5N1-Specific T-Cell Responses in a High-risk Cohort in Vietnam Indicates the Existence of Potential Asymptomatic Infections

[tetano]

J Infect Dis. 2011 Nov 11. [Epub ahead of print]
Identification of H5N1-Specific T-Cell Responses in a High-risk Cohort in Vietnam Indicates the Existence of Potential Asymptomatic Infections.
Powell TJ, Fox A, Peng Y, Quynh Mai LT, Lien VT, Hang NL, Wang L, Lee LY, Simmons CP, McMichael AJ, Farrar JJ, Askonas BA, Duong TN, Thai PQ, Thu Yen NT, Rowland-Jones SL, Hien NT, Horby P, Dong T.
Source

MRC Human Immunology Unit, University of Oxford, John Radcliffe Hospital, United Kingdom.
Abstract

Background. Most reported human H5N1 viral infections have been severe and were detected after hospital admission. A case ascertainment bias may therefore exist, with mild cases or asymptomatic infections going undetected. We sought evidence of mild or asymptomatic H5N1 infection by examining H5N1-specific T-cell and antibody responses in a high-risk cohort in Vietnam.Methods. Peripheral blood mononuclear cells were tested using interferon-γ enzyme-linked immunospot T assays measuring the response to peptides of influenza H5, H3, and H1 hemagglutinin (HA), N1 and N2 neuraminidase, and the internal proteins of H3N2. Horse erythrocyte hemagglutination inhibition assay was performed to detect antibodies against H5N1.Results. Twenty-four of 747 individuals demonstrated H5-specific T-cell responses but little or no cross-reactivity with H3 or H1 HA peptides. H5N1 peptide-specific T-cell lines that did not cross-react with H1 or H3 influenza virus HA peptides were generated. Four individuals also had antibodies against H5N1.Conclusions. This is the first report of ex vivo H5 HA-specific T-cell responses in a healthy but H5N1-exposed population. Our results indicate that the presence of H5N1-specific T cells could be an additional diagnostic tool for asymptomatic H5N1 infection.

PMID:
22080094
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/22080094

 

[tetano]

Re: Identification of H5N1-Specific T-Cell Responses in a High-risk Cohort in Vietnam Indicates the Existence of Potential Asymptomatic Infections

T-Cell Immune Responses and Asymptomatic H5N1 Influenza Infection

Suzanne Epstein


Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, Maryland

Correspondence: Suzanne Epstein, PhD, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, HFM-730, Rockville, MD 20852 (suzanne.epstein@fda.hhs.gov).

ARTICLE

Approximately 60% of people ill with influenza A virus subtype H5N1 infection die [1], a case fatality rate about 25 times worse than that during the 1918 pandemic [2]. It is hard to even imagine the devastation that would result if such a virus spread widely. However, as discussed by many, the case fatality rate might decline with adaptation to transmission. Even now, H5N1 cases may be underreported (and hence the case fatality rate may be overestimated) because some infections are mild or asymptomatic. Questions about the real frequency of H5N1 infection, and thus the case fatality rate have led to seroprevalence surveys. In areas where H5N1 outbreaks have recently occurred, results show low numbers of seropositive people whose infections must have been asymptomatic or mild [3, 4].

Are such surveys missing H5N1 infections by screening only for antibody? Using antibody as a marker of infection has practical advantages but also limitations, including assay technical issues and low immunogenicity of H5 hemagglutinin (HA) for antibody responses [5]. In this issue of the Journal, the group of Tao Dong at Oxford University (Powell et al) investigated another option. They asked whether assays for T-cell immunity to H5 HA can be used to detect asymptomatic infections. In the past, large-scale population screening for T-cell responses would have been an overwhelming technical challenge. It is still a major effort, but it is now feasible to screen large numbers of human subjects for T-cell responses to overlapping peptide libraries spanning viral antigens.

Powell et al screened a Vietnamese cohort of 747 people with potential asymptomatic H5N1 exposure due to occasional avian and human H5N1 outbreaks nearby in the preceding few years. They used T-cell interferon-γ enzyme-linked immunosorbent spot (ELISPOT) assays with peptide pools ?

http://jid.oxfordjournals.org/content/early/2011/11/10/infdis.jir692.short