The role of T cells in mediating heterosubtypic protection against natural influenza illness in humans is uncertain. The 2009 H1N1 pandemic (pH1N1) provided a unique natural experiment to determine whether crossreactive cellular immunity limits symptomatic illness in antibody-naive individuals. We followed 342 healthy adults through the UK pandemic waves and correlated the responses of pre-existing T cells to the pH1N1 virus and conserved core protein epitopes with clinical outcomes after incident pH1N1 infection. Higher frequencies of pre-existing T cells to conserved CD8 epitopes were found in individuals who developed less severe illness, with total symptom score having the strongest inverse correlation with the frequency of interferon-γ (IFN-γ)(+) interleukin-2 (IL-2)(-) CD8(+) T cells (r = -0.6, P = 0.004). Within this functional CD8(+)IFN-γ(+)IL-2(-) population, cells with the CD45RA(+) chemokine (C-C) receptor 7 (CCR7)(-) phenotype inversely correlated with symptom score and had lung-homing and cytotoxic potential. In the absence of crossreactive neutralizing antibodies, CD8(+) T cells specific to conserved viral epitopes correlated with crossprotection against symptomatic influenza. This protective immune correlate could guide universal influenza vaccine development.

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Vaccination of health care workers (HCWs) is recommended as a strategy for preventing influenza in elderly patients in long-term care. However, there have been no controlled studies to show whether this approach is effective. During the winter of 1994-1995, 1059 patients in 12 geriatric medical long-term-care sites, randomized for vaccination of HCWs, were studied. In hospitals where HCWs were offered vaccination, 653 (61%) of 1078 were vaccinated. Vaccination of HCWs was associated with reductions in total patient mortality from 17% to 10% (odds ratio [OR], 0.56; 95% confidence interval [CI], 0.40-0.80) and in influenza-like illness (OR, 0.57; 95% CI, 0.34-0.94). Vaccination of patients was not associated with significant effects on mortality (OR, 1.15; 95% CI, 0.81-1.64). Results of this study support recommendations for vaccination against influenza of HCWs in long-term geriatric care. Vaccination of frail elderly long-term-care patients may not give clinically worthwhile benefits.

Hepatitis B surface antigen (HBsAg) is not only critical to the biology of hepatitis B virus (HBV), it is also the basis of the currently available vaccines, assays to detect it in serum are crucial for diagnosis of infection and antibodies against it are used clinically to suppress infection of transplanted livers. All of these rely on antigenic interactions between HBsAg and HBsAb. Thus, it should not be surprise that changes in epitopes will affect all these situations. It is useful to classify such changes simplistically as variants, found in natural isolates, and mutants, which are observed to emerge, usually under immunological pressure, often medical in origin. The former tend to affect the sensitivity of diagnostic assays and the latter allow escape of viruses in vaccinees and those being treated with HBsAb. The majority of these changes cluster in the hydrophilic central core of HBsAg, from aa99 up to 169. They are gaining importance as causes of mistaken diagnosis and are associated with infection of vaccinees and transplanted livers. There is a danger that they will become the dominant strains as vaccination becomes universal. More data are required on the epidemiology and antigenicity of these changes.

Patients with primary biliary cirrhosis develop progressive ductopenia associated with the production of antimitochondrial antibodies that react with a protein aberrantly expressed on biliary epithelial cells and peri-hepatic lymph nodes. Although no specific microbe has been identified, it is thought that an infectious agent triggers this autoimmune liver disease in genetically predisposed individuals. Previous serologic studies have provided evidence to suggest a viral association with primary biliary cirrhosis. Here we describe the identification of viral particles in biliary epithelium by electron microscopy and the cloning of exogenous retroviral nucleotide sequences from patients with primary biliary cirrhosis. The putative agent is referred to as the human betaretrovirus because it shares close homology with the murine mammary tumor virus and a human retrovirus cloned from breast cancer tissue. In vivo, we have found that the majority of patients with primary biliary cirrhosis have both RT-PCR and immunohistochemistry evidence of human betaretrovirus infection in lymph nodes. Moreover, the viral proteins colocalize to cells demonstrating aberrant autoantigen expression. In vitro, we have found that lymph node homogenates from patients with primary biliary cirrhosis can induce autoantigen expression in normal biliary epithelial cells in coculture. Normal biliary epithelial cells also develop the phenotypic manifestation of primary biliary cirrhosis when cocultivated in serial passage with supernatants containing the human betaretrovirus or the murine mammary tumor virus, providing a model to test Koch's postulates in vitro.

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Medical Research Council.