Mapping Host-Related Correlates of Influenza Vaccine-Induced Immune Response: An Umbrella Review of the Available Systematic Reviews and Meta-Analyses.

Seasonal influenza is the leading infectious disease in terms of its health and socioeconomic impact. Annual immunization is the most efficient way to reduce this burden. Several correlates of influenza vaccine-induced protection are commonly used, owing to their ready availability and cheapness. Influenza vaccine-induced immunogenicity is a function of host-, virus- and vaccine-related factors. Host-related factors constitute the most heterogeneous group. The objective of this study was to analyze the available systematic evidence on the host factors able to modify influenza vaccine-induced immunogenicity. An umbrella review approach was undertaken. A total of 28 systematic reviews/meta-analyses were analyzed-these covered the following domains: intravenous drug use, psychological stress, acute and chronic physical exercise, genetic polymorphisms, use of pre-/pro-/symbiotics, previous Bacillus Calmette-Guérin vaccination, diabetes mellitus, vitamin D supplementation/deficiency, latent cytomegalovirus infection and various forms of immunosuppression. In order to present effect sizes on the same scale, all possible meta-analyses were re-performed and cumulative evidence synthesis ranking was carried out. The meta-analysis was conducted separately on each health condition category and virus (sub)type. A total of 97 pooled estimates were used in order to construct an evidence-based stakeholder-friendly map. The principal public health implications are discussed.

Flucelvax (Optaflu) for seasonal influenza.

Conventional egg-based manufacturing technology for seasonal influenza vaccines has several drawbacks, including its inflexibility, reliance on egg supplies, risk of contamination, absence of growth of some isolates and egg-adaptive viral mutations that threaten vaccine matching. To overcome these limitations, cell culture-derived vaccines have been designed, including the trivalent inactivated vaccine Flucelvax®/Optaflu® (brand names in the US/EU, respectively). Flucelvax®/Optaflu® has gained wide regulatory approval and is currently implemented in several countries. Non-clinical studies have assuaged hypothetical concerns regarding oncogenicity and use in persons allergic to dogs. Ample clinical data suggest the non-inferiority of Flucelvax®/Optaflu® to egg-based vaccines in terms of immunogenicity, safety and tolerability, and it has fulfilled American and European mandatory requirements. Although Flucelvax®/Optaflu® is currently indicated only for adults and the elderly, pediatric data indicate its good immunogenicity and safety. This paper provides an update on the clinical development of Flucelvax®/Optaflu®, its seasonal trials and available post-marketing surveillance data.

Combination adjuvants for the induction of potent, long-lasting antibody and T-cell responses to influenza vaccine in mice.

Influenza is controlled by protective titres of neutralizing antibodies, induced with the help of CD4 T-cells, and by antiviral T-cell effector function. Adjuvants are essential for the efficient vaccination of a naïve population against avian influenza. We evaluated a range of adjuvants for their ability to enhance, in naïve mice, protective hemagglutination inhibition (HI) titres, which represent the generally accepted correlate of protection, virus-neutralizing titres and T-cell responses to a new generation influenza vaccine produced in cell culture. The selected adjuvants include alum, calcium phosphate (CAP), MF59, the delivery system poly-(lactide co-glycolide) (PLG) and the immune potentiator CpG. MF59 was clearly the most potent single adjuvant and induced significantly enhanced, long-lasting HI and neutralizing titres and T-cell responses in comparison to all alternatives. The combination of alum, MF59, CAP or PLG with CpG generally induced slightly more potent titres. The addition of CpG to MF59 also induced a more potent Th1 cellular immune response, represented by higher IgG2a titres and the induction of a strongly enhanced IFN-gamma response in splenocytes from immunized mice. These observations have significant implications for the development of new and improved flu vaccines against pandemic and inter-pandemic influenza virus strains.