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To combat the possibility of a zoonotic H5N1 pandemic in a timely fashion, it is necessary to develop a vaccine that would confer protection against homologous and heterologous human H5N1 influenza viruses. Using a replicating modified vaccinia virus Tian Tan strain (MVTT) as a vaccine vector, we constructed MVTTHA-QH and MVTTHA-AH, which expresses the H5 gene of a goose-derived Qinghai strain A/Bar-headed Goose/Qinghai/1/2005 or human-derived Anhui Strain A/Anhui/1/2005. The immunogenicity profiles of both vaccine candidates were evaluated. Vaccination with MVTTHA-QH induced a significant level of neutralizing antibodies (Nabs) against a homologous strain and a wide range of H5N1 pseudoviruses (clades 1, 2.1, 2.2, 2.3.2, and 2.3.4). Neutralization tests (NT) and Haemagglutination inhibition (HI) antibodies inhibit the live autologous virus as well as a homologous A/Xingjiang/1/2006 and a heterologous A/Vietnam/1194/2004, representing two human isolates from clade 2.2 and clade 1, respectively. Importantly, mice vaccinated with intranasal MVTTHA-QH were completely protected from challenge with lethal dosages of A/Bar-headed Goose/Qinghai/1/2005 and the A/Viet Nam/1194/2004, respectively, but not control mice that received a mock MVTTS vaccine. However, MVTTHA-AH induced much lower levels of NT against its autologous strain. Our results suggest that it is feasible to use the H5 gene from A/Bar-headed Goose/Qinghai/1/2005 to construct an effective vaccine, when using MVTT as a vector, to prevent infections against homologous and genetically divergent human H5N1 influenza viruses.

ABSTRACT. The aim of this study was to investigate the characteristics and polymorphisms of the T-cell receptor BV complementaritydetermining region 3 (TCR BV CDR3) gene in peripheral blood mononuclear cells (PBMCs) from patients with uveitis to provide an experimental basis for studying the pathogenesis of this disease. RT-PCR amplification of 26 subfamilies of the TCR BV CDR3 gene and immune spectratyping analysis were used to study the pedigree drift of TCR BV CDR3 in PBMCs from the uveitis patients. The following results were obtained: 1) the vast majority of the TCR BV CDR3 spectra in PBMCs in 5 healthy subjects fit the normal (or Gaussian) distribution. The distributions of the TCR BV CDR3 spectra in 4 patients with uveitis were non-normal and showed an abnormal peak including a widowed peak trend, a partial peak, and an irregular abnormal peak. 2) In the 26 TCR BV subfamilies, the abnormal peak frequency was different T-cell receptor and uveitis in the various subfamilies. The BV2 and BV17 (both 3/4) subfamilies had higher frequencies of the non-normally distributed abnormal peak. The BV5.2, BV6, BV15, and BV18 subfamilies showed no abnormal peaks. 3) TCR BV2 and BV17 yielded an abnormal peak in 3 HLA-B27-negative patients; however, no such abnormalities were detected in HLA-B27-positive patients. The abnormal expression of some TCR BV subfamilies in PBMCs from patients with uveitis may be associated with the immune pathogenesis of the disease. Our study provides the basis for further investigations into the pathogenesis of uveitis.