Immunogenicity and safety of trivalent versus quadrivalent seasonal influenza vaccine : a systematic review

Abstract

The substantial burden on health care and society due to seasonal influenza epidemic is well evident and is further aggravated by continuous mismatch of B linage, between circulating B linage and trivalent vaccine (TIV) contained B linages, across all ages. As such World Health Organization (WHO) recommended to include additional B linages in the seasonal influenza vaccine in 2013, since then increased trend for quadrivalent influenza vaccine (QIV) has been observed among most of the developed countries to broaden the protection against all four influenza strains. But considerable uncertainty still remains to use QIV over TIV, due to limited evidence on immunogenicity and safety of QIV versus TIV. Hence assessing non-inferiority of QIV versus TIV in terms of immunogenicity and comparable safety profile of QIV versus TIV in this systematic review, provides solid evidence for selection of seasonal influenza vaccine for all ages in terms of preventing flu epidemic around the world.

The studies only in the English language were identified searching “PubMed” data base using EndNote software without a defined time period. The descriptive immunogenicity of QIV and TIV were assessed for criteria recommended by the Centre for Biologics Evaluation and Research (CBER) /Committee for Medicinal Products for Human Use (CHMP) in terms of post vaccination percentage of Sero Conversion Rate (SCR%), Sero Protection Rate (SPR%), Sero Conversion Factor (SCF) value and Geometric Mean Titer (GMT) value from Heamagglutination Inhibition (HI) assay. The non-inferiority for shared strain and superiority for alternate B linage of QIV versus TIV was assessed by the GMT ratio with 95%CI. The SCR difference was used as an optional criteria for assessing non-inferiority and superiority of QIV versus TIV. The solicited injection site and general adverse events (AE), Serious AEs and Medical attended AEs were safety outcomes.

Twelve Randomized Controlled Trials were identified across three age groups as infants<47 months, children<17 years and adults >18 years old. The inactivated, adjuvant (AD) and live attenuated (LA) formulation of both QIV and TIV were included. The intramuscular (IM), intradermal (ID) and intranasal route were identified as route of administration of both vaccines across all studies. All QIVs in children and adults met CBER criteria against four influenza strain, except study on infant where this criteria was not applicable. All TIVs met given criteria for both types A strains and homologous B linages as a vaccine strain in children 3-17yeras and adults>18 years except one study. QIV was shown to be more immunogenic against alternate B linage compared to TIV both in children and adults in terms of terms of post vaccination GMT value, SCR% and SCF value. This observation was more notable in children 3-17 years compared to adults >18 years. Elderly groups> 61 years elicited lower post vaccination GMT and SCF value compared to adults18-60 years for all three vaccine types. QIV shown to be non-inferior to TIV for shared strain and superior for alternate B linage in terms of adjusted GMT ratio for all ages except two studies in infant<48 months and one study in children 3- 9 years. These findings were not different with either vaccine formulation (inactivated, AD and LA) or route of administration of vaccine (IM, ID and intranasal) in children 3-17yeras and adults>18 years. There was no marked difference in reactogenicity between QIV and TIV for all age groups. The finding was not different with either formulation (AD, LA) or route of administrations (IM, ID and intranasal) of vaccine in children<17 years and adults>18 year. But the adjuvant formulation of both QIV and TIV showed higher reactogenicity compared to non-adjuvant formulation in adults >18 years. Hence vaccination policy with QIV, as a means of preventing seasonal influenza epidemic is strongly encouraged as it gives broder protection than TIV, against both B linages in child<17 years and adults>18 years, though there are still inconsistency of non-inferiority of QIV vs TIV in infants<48 months. It should benefit health care and society from substantial reductions in burden of B linages mismatch. But limited evidence is available on the degree of reduction in this burden in literature. This should be supported by cost utility/effectiveness studies on QIV versus TIV. It suggest to establish criteria exist for evaluating seasonal influenza vaccine in infancy.