Inactivated and Adjuvanted Influenza Vaccines

Abstract

Inactivated influenza vaccines are produced every year to fight against the seasonal epidemics of influenza. Despite the nonoptimal coverage, even in subjects at risk like the elderly, pregnant women, etc., these vaccines significantly reduce the burden of mortality and morbidity linked to the influenza infection. Importantly, these vaccines have also contributed to reduce the impact of the last pandemics. Nevertheless, the performance of these vaccines can be improved mainly in those age groups, like children and the elderly, in which their efficacy is suboptimal. The use of adjuvants has proven effective to this scope. Oil-in-water adjuvants like MF59 and AS03 have been licensed and widely used, and shown efficacious in preventing influenza infection in the last pandemic. MF59-adjuvanted inactivated vaccine was more efficacious than non-adjuvanted vaccine in preventing influenza infection in young children and in reducing hospitalization due to the influenza infection in the elderly. Other adjuvants are now at different stages of development and some are being tested in clinical trials. The perspective remains to improve the way inactivated vaccines are prepared and to accelerate their availability, mainly in the case of influenza pandemics, and to enhance their efficacy/effectiveness for a more successful impact at the public health level.

The immune correlates of protection for an avian influenza H5N1 vaccine in the ferret model using oil-in-water adjuvants

“…Both are squalene-based emulsions that act by stimulating a local inflammatory environment, although AS03 has an added component of α-tocopherol (Vitamin E), an immunostimulant31 that was important for its potent adjuvant effect32. However, this difference in potency is negligible when antigen concentration is increased9.…”

Evaluation of the innate immune responses to influenza and live-attenuated influenza vaccine infection in primary differentiated human nasal epithelial cells

“…Although vaccination remains the best approach against infection and disease, the identification of new circulating strains and the time for production and distribution present constraints on vaccine development. Additionally, other host-driven factors can contribute to the efficacy of influenza vaccines (Del Giudice and Rappuoli, 2015). Defining host molecular responses—and the viral and host factors interactions that trigger and regulate them—is therefore essential to developing effective vaccines.…”

Immunogenicity and safety of concomitant MF59-adjuvanted influenza vaccine and 23-valent pneumococcal polysaccharide vaccine administration in older adults

“…MF59 enhances the immune responses to vaccine antigens both quantitatively and qualitatively [6]. After intramuscular inoculation, the nanoemulsion stimulates an influx of inflammatory cells (granulocytes, monocytes and macrophages) to the injection site, the release of chemokines, including CCL2, 3, 4, and IL18, as well as the activation of macrophage, resulting in an increase in uptake of co-administered antigens [11,12].…”

“…MF59 emulsion-adjuvanted trivalent inactivated influenza vaccine (aIIV3) may provide higher and broader antibody responses than conventional IIV3, resulting in a higher level of clinical http effectiveness [6][7][8][9][10]. The adjuvanted seasonal vaccine is licensed in numerous European, Asian and Latin American countries and in Canada specifically for older adults, for whom the pneumococcal vaccine also may be recommended.…”