Children aged 7–14 years in Novgorod, Russia, were given Russian live cold-adapted or inactivated influenza vaccines or placebo over a 2-year period. Schools were randomly assigned as a whole to one of the preparations. In the first year, the vaccines were bivalent, containing types A (H3N2) and A (H1N1) components. In the second year, the vaccines also contained a type B component. In the first year, all viruses isolated were type A (H3N2); in the second, about three-quarters of the isolates were type B and the rest type A (H1N1). During both years, the vaccines protected the vaccinated children. Where significant differences existed, the live attenuated vaccine was more protective than the inactivated. Vaccination rates in schools in which live attenuated vaccines had been used were inversely related to illness rates of staffand unvaccinated children, suggesting that viral transmission had been reduced by the vaccine.

Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double–blinded randomized placebo–controlled phase I clinical trial of cold–adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults. The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential. Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person–to–person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two–dose immunization resulted in measurable serum and local antibody production and in generation of antigen–specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus–specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells. The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus. ClinicalTrials.gov NCT01511419

One of the essential mechanisms of virus infection control is cell-mediated cytotoxicity, which can act in an antibody-dependent or -independent fashion and is provided by different effector cells. The role of CD8 T-cells in infection control and in affecting the pathological outcome of different types of infection has been demonstrated in numerous animal studies. Despite this, their role in controlling human influenza infection is not fully understood. Especially, knowledge about their induction and turnover in human influenza infection is limited. Differences in the development of CD8 T-cells after influenza infection or immunizations should be explored in detail, in relation to the bioaccessibility of influenza antigens, site of application and distribution routes. This review focuses on the basics of CD8 T-cell immune response both in human influenza infection and after administration of inactivated or live attenuated influenza vaccine. Some aspects of the accessibility, distribution and presentation of influenza antigens to CD8 T-cells are described. The CD8 T-cell response is an essential connection between innate and antibody-mediated responses, which are all-important for influenza control. We hypothesize that immunization with live influenza vaccine is the most straightforward artificial way to induce an efficient influenza-specific CD8 T-cell response.