Abstract
Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements in vaccine design are needed to increase the strength, breadth, and duration of immunity against diverse strains that circulate during regular epidemics, occasional pandemics, and from animal reservoirs. Universal vaccine strategies that target more conserved regions of the virus, such as the hemagglutinin (HA)-stalk, or recruit other cellular responses, such as T cells and NK cells, have the potential to provide broader immunity. Many pre-pandemic vaccines in clinical development do not utilize new vaccine platforms but use “tried and true” recombinant HA protein or inactivated virus strategies despite substantial leaps in fundamental research on universal vaccines. Significant hurdles exist for universal vaccine development from bench to bedside, so that promising preclinical data is not yet translating to human clinical trials. Few studies have assessed immune correlates derived from asymptomatic influenza virus infections, due to the scale of a study required to identity these cases. The realization and implementation of a universal influenza vaccine requires identification and standardization of set points of protective immune correlates, and consideration of dosage schedule to maximize vaccine uptake.
Highlights
Influenza A viruses have over 18 different hemagglutinin (HA) subtypes, and continual antigenic drift of seasonal H3N2 and H1N1 viruses generates new variants
Local Secreted IgA (sIgA) not serum Hemagglutination inhibition (HAI) correlates with protection from symptomatic infection Increased T cell responses, not HAI, and IFNγ:IL-10 ratio correlated with reduced risk of infection in the elderly HAI has limited value when viruses mismatched, NAI correlated with reduced infection cases
live-attenuated influenza vaccines (LAIV) was effective against natural H3N2 and FluB infection, and H1N1 challenge due to higher titers of strain-specific sIgA >100 SFU/106 PBMC protected from symptomatic infection LAIV variably induces strain-specific sIgA which correlates with reduced symptomatic infection T cell activating vaccine reduced symptom severity and viral shedding 2 dose P-Inactivated influenza vaccines (IIV) had 100% protection against symptomatic infection
Summary
Influenza A viruses have over 18 different hemagglutinin (HA) subtypes, and continual antigenic drift of seasonal H3N2 and H1N1 viruses generates new variants. There are distinct lineages of influenza B viruses that exhibit antigenic drift, meaning there is a plethora of influenza viruses that pose a threat to public health [1]. Influenza vaccines are the most widely used vaccines in the world due to annual updates on circulating strains and health authority recommendations for at risk groups [4]. The groups most commonly targeted for influenza vaccination programs are children and elderly, pregnant women, immunocompromised, and healthcare workers (HCWs).
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