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Background: We investigated the contribution of age, coexisting medical conditions, sex, and vaccination to incidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and of severe, critical, or fatal COVID‐19 in older adults since pandemic onset. Methods: A national retrospective cohort study was conducted in the population of Qatar aged ≥50 years between February 5, 2020 and June 15, 2023. Adjusted hazard ratios (AHRs) for infection and for severe coronavirus disease 2019 (COVID‐19) outcomes were estimated through Cox regression models. Results: Cumulative incidence was 25.01% (95% confidence interval [CI]: 24.86–25.15%) for infection and 1.59% (95% CI: 1.55–1.64%) for severe, critical, or fatal COVID‐19 after a follow‐up duration of 40.9 months. Risk of infection varied minimally by age and sex but increased significantly with coexisting conditions. Risk of infection was reduced with primary‐series vaccination (AHR: 0.91, 95% CI: 0.90–0.93) and further with first booster vaccination (AHR: 0.75, 95% CI: 0.74–0.77). Risk of severe, critical, or fatal COVID‐19 increased exponentially with age and linearly with coexisting conditions. AHRs for severe, critical, or fatal COVID‐19 were 0.86 (95% CI: 0.7–0.97) for one dose, 0.15 (95% CI: 0.13–0.17) for primary‐series vaccination, and 0.11 (95% CI: 0.08–0.14) for first booster vaccination. Sensitivity analysis restricted to only Qataris yielded similar results. Conclusion: Incidence of severe COVID‐19 in older adults followed a dynamic pattern shaped by infection incidence, variant severity, and population immunity. Age, sex, and coexisting conditions were strong determinants of infection severity. Vaccine protection against severe outcomes showed a dose–response relationship, highlighting the importance of booster vaccination for older adults. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Sarah C. Gilbert. (2012) Advances in the development of universal influenza vaccines. Influenza and Other Respiratory Viruses DOI:10.1111/irv.12013. Despite the widespread availability and use of influenza vaccines, influenza still poses a considerable threat to public health. Vaccines against seasonal influenza do not offer protection against pandemic viruses, and vaccine efficacy against seasonal viruses is reduced in seasons when the vaccine composition is not a good match for the predominant circulating viruses. Vaccine efficacy is also reduced in older adults, who are one of the main target groups for vaccination. The continual threat of pandemic influenza, with the known potential for rapid spread around the world and high mortality rates, has prompted researchers to develop a number of novel approaches to providing immunity to this virus, focusing on target antigens which are highly conserved between different influenza A virus subtypes. Several of these have now been taken into clinical development, and this review discusses the progress that has been made, as well as considering the requirements for licensing these new vaccines and how they might be used in the future. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Zambon. (2012) Surveillance for antiviral resistance. Influenza and Other Respiratory Viruses 7(Suppl. 1), 37-43. In the 10 years since licensure of neuraminidase inhibitor drugs, their use has steadily increased, especially during the pandemic of 2009. Experience now indicates that factors which influence the emergence of high level resistance include the nature of drug binding to target, viral subtype, the use of post exposure prophylaxis and a lack of immunity in the host as seen in children and immunocompromised individuals. These factors point towards targetted surveillance programmes for the early identification of transmissible drug resistance. [ABSTRACT FROM AUTHOR]

Please cite this paper as: De Vleeschauwer et al. (2011) Cross-protection between antigenically distinct H1N1 swine influenza viruses from Europe and North America. Influenza and Other Respiratory Viruses 5(2), 115-122. An avian-like H1N1 swine influenza virus (SIV) is enzootic in swine populations of Western Europe. The virus is antigenically distinct from H1N1 SIVs in North America that have a classical swine virus-lineage H1 hemagglutinin, as does the pandemic (H1N1) 2009 virus. However, the significance of this antigenic difference for cross-protection among pigs remains unknown. We examined protection against infection with a North American triple reassortant H1N1 SIV [A/swine/Iowa/H04YS2/04 (sw/IA/04)] in pigs infected with a European avian-like SIV [A/swine/Belgium/1/98 (sw/B/98)] 4 weeks earlier. We also examined the genetic relationships and serologic cross-reactivity between both SIVs and with a pandemic (H1N1) 2009 virus [A/California/04/09 (Calif/09)]. After intranasal inoculation with sw/IA/04, all previously uninfected control pigs showed nasal virus excretion, high virus titers in the entire respiratory tract at 4 days post-challenge (DPCh) and macroscopic lung lesions. Most pigs previously infected with sw/B/98 tested negative for sw/IA/04 in nasal swabs and respiratory tissues, and none had lung lesions. At challenge, these pigs had low levels of cross-reactive virus neutralizing and neuraminidase inhibiting (NI) antibodies to sw/IA/04, but no hemagglutination-inhibiting antibodies. They showed similar antibody profiles when tested against Calif/09, but NI antibody titers were higher against Calif/09 than sw/IA/04, reflecting the higher genetic homology of the sw/B/98 neuraminidase with Calif/09. Our data indicate that immunity induced by infection with European avian-like H1N1 SIV affords protection for pigs against North American H1N1 SIVs with a classical H1, and they suggest cross-protection against the pandemic (H1N1) 2009 virus. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Pearce et al. (2011) Understanding mortality in the 1918-1919 influenza pandemic in England and Wales. Influenza and Other Respiratory Viruses 5(2), 89-98. The causes of recurrent waves in the 1918-1919 influenza pandemic are not fully understood. To identify the risk factors for influenza onset, spread and mortality in waves 1, 2 and 3 (summer, autumn and winter) in England and Wales in 1918-1919. Influenza mortality rates for 333 population units and putative risk factors were analysed by correlation and by regressions weighted by population size and adjusted for spatial trends. For waves 1 and 3, influenza mortality was higher in younger, northerly and socially disadvantaged populations experiencing higher all-cause mortality in 1911-1914. Influenza mortality was greatest in wave 2, but less dependent on underlying population characteristics. Wave duration was shorter in areas with higher influenza mortality, typically associated with increasing population density. Regression analyses confirmed the importance of geographical factors and pre-pandemic mortality for all three waves. Age effects were complex, with the suggestion that younger populations with greater mortality in wave 1 had lesser mortality in wave 2. Our findings suggest that socially disadvantaged populations were more vulnerable, that older populations were partially protected by prior immunity in wave 1 and that exposure of (younger) populations in one wave could protect against mortality in the subsequent wave. An increase in viral virulence could explain the greater mortality in wave 2. Further modelling of causal processes will help to explain, in considerable detail, how social and geographical factors, season, pre-existing and acquired immunity and virulence affected viral transmission and pandemic mortality in 1918-1919. [ABSTRACT FROM AUTHOR]

Please cite this paper as: Kash et al. (2010) Prior infection with classical swine H1N1 influenza viruses is associated with protective immunity to the 2009 pandemic H1N1 virus. Influenza and Other Respiratory Viruses 4(3), 121–127. Background The 2009 H1N1 pandemic emerged even though seasonal H1N1 viruses have circulated for decades. Epidemio-logical evidence suggested that the current seasonal vaccine did not offer significant protection from the novel pandemic, and that people over the age of 50 might were less susceptible to infection. Objectives In a mouse challenge study with the 2009 pandemic H1N1 virus, we evaluated protective immune responses elicited by prior infection with human and swine influenza A viruses. Results Mice infected with A/Mexico/4108/2009 (Mex09) showed significant weight loss and 40% mortality. Prior infection with a 1976 classical swine H1N1 virus resulted in complete protection from Mex09 challenge. Prior infection with either a 2009 or a 1940 seasonal H1N1 influenza virus provided partial protection and a >100-fold reduction in viral lung titers at day 4 post-infection. Conclusions These findings indicate that in experimental animals recently induced immunity to 1918-derived H1N1 seasonal influenza viruses, and to a 1976 swine influenza virus, afford a degree of protection against the 2009 pandemic virus. Implications of these findings are discussed in the context of accumulating data suggesting partial protection of older persons during the 2009 pandemic. [ABSTRACT FROM AUTHOR]

Background The best form of protection against influenza is high-titred virus-neutralizing antibody specific for the challenge strain. However, this is not always possible to achieve by vaccination due to the need for predicting the emerging virus, whether it be a drift variant of existing human endemic influenza type A subtypes or the next pandemic virus, for incorporation into the vaccine. By activating additional arms of the immune system to provide heterosubtypic immunity, that is immunity active against all viruses of type A influenza regardless of subtype or strain, it should be possible to provide significant benefit in situations where appropriate antibody responses are not achieved. Although current inactivated vaccines are unable to induce heterosubtypic CD8+ T cell immunity, we have shown that lipopeptides are particularly efficient in this regard. Objectives To examine the role of vaccine-induced CD8+ T cells in altering the course of disease due to highly virulent H1N1 influenza virus in the mouse model. Methods The induction of influenza-specific CD8+ T cells following intranasal inoculation with lipopeptide vaccine was assessed by intracellular cytokine staining (ICS) and the capacity of these cells to reduce viral loads in the lungs and to protect against death after viral challenge was determined. Results and conclusions We show that CD8+ T cells are induced by a single intranasal vaccination with lipopeptide, they remain at substantial levels in the lungs and are efficiently boosted upon challenge with virulent virus to provide late control of pulmonary viral loads. Vaccinated mice are not only protected from death but remain active, indicative of less severe disease despite significant weight loss. [ABSTRACT FROM AUTHOR]

The current pandemic threat can be best understood within an ecological framework that takes account of the history of past pandemics caused by influenza A, the relationships between pandemic and seasonal spread of influenza viruses, and the importance of immunity and behavioural responses in human populations. Isolated populations without recent exposure to seasonal influenza seem more susceptible to new pandemic viruses, and much collateral evidence suggests that this is due to immunity directed against epitopes shared between pandemic and previously circulating strains of inter-pandemic influenza A virus. In the highly connected modern world, most populations are regularly exposed to non-pandemic viruses, which can even boost immunity without causing influenza symptoms. Such naturally-induced immunity helps to explain the low attack-rates of seasonal influenza, as well as the moderate attack-rates in many urbanized populations affected by 1918–1919 and later pandemics. The effectiveness of immunity, even against seasonal influenza, diminishes over time because of antigenic drift in circulating viruses and waning of post-exposure immune responses. Epidemiological evidence suggests that cross-protection against a new pandemic strain could fade even faster. Nevertheless, partial protection, even of short duration, induced by prior seasonal influenza or vaccination against it, could provide important protection in the early stages of a new pandemic. [ABSTRACT FROM AUTHOR]

Objective Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402-6/86(H5N2) virus and the cold-adapted ( ca) donor strain A/Leningrad/134/17/57(H2N2). Methods During Phase I–II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post-vaccination. Serum antibody responses were measured by hemagglutination-inhibition and microneutralization and local antibodies were estimated using an enzyme-linked immunosorbent assay test. Results The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47·1–54·8% of subjects showed ≥fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29·4–30·8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 × PR8 IBCDC-RG (H5N1). Virus-neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus-specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of ≥fourfold rise SIgA antibodies (65%) geometrical mean titers (16·0) and a rise in SIgA antibodies (2·8) compared with one dose. Conclusion The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross-reactivity to the A(H5N1) strain in the HAI test. [ABSTRACT FROM AUTHOR]

Vaccination is considered to be one of the most effective tools to decrease morbidity as well as mortality caused by influenza viruses. For the prevention of seasonal influenza, Fluarix ™ and FluLaval™ have been marketed since 1987 and 1992, respectively. Both vaccines have consistently been shown to meet or exceed the regulatory criteria for immunogenicity against the three strains H1N1, H3N2 and B, have a good safety profile, and are recommended for vaccinating children and adults of all ages. For the prevention of pandemic influenza, GlaxoSmithKline (GSK) has obtained licensure of a pre-pandemic vaccine, Prepandrix ™. This split-virus H5N1 adjuvanted with AS03, a proprietary oil-in-water emulsion-based adjuvant system, has demonstrated broad immunity against drifted H5N1 strains and has been shown to be effective in preventing mortality and viral shedding in animal studies. The influenza vaccine portfolio of GSK addresses specific medical needs related to seasonal or pandemic influenza viruses, which remain an important public health threat worldwide. [ABSTRACT FROM AUTHOR]