Abstract
Avian influenza viruses from the A/H5 A/goose/Guangdong/1/1996 (GsGd) lineage pose a continuing threat to animal and human health. Since their emergence in 1997, these viruses have spread across multiple continents and have become enzootic in poultry. Additionally, over 800 cases of human infection with A/H5 GsGd viruses have been reported to date, which raises concerns about the potential for a new influenza virus pandemic. The continuous circulation of A/H5 GsGd viruses for over 20 years has resulted in the genetic and antigenic diversification of their hemagglutinin (HA) surface glycoprotein, which poses a serious challenge to pandemic preparedness and vaccine design. In the present article, clinical studies on A/H5 influenza vaccination strategies were reviewed to evaluate the breadth of antibody responses induced upon homologous and heterologous prime-boost vaccination strategies. Clinical data on immunological endpoints were extracted from studies and compiled into a dataset, which was used for the visualization and analysis of the height and breadth of humoral immune responses. Several aspects leading to high immunogenicity and/or cross-reactivity were identified, although the analysis was limited by the heterogeneity in study design and vaccine type used in the included studies. Consequently, crucial questions remain to be addressed in future studies on A/H5 GsGd vaccination strategies.
Highlights
Influenza A viruses pose a significant global burden on human and animal health.They are divided into subtypes based on the antigenic properties of their surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA)
The height and breadth of antibody responses induced by homologous prime-boost vaccination strategies with
A/H5 influenza vaccines were visualized by plotting vaccination strategies with A/H5 influenza vaccines were visualized by plotting the im-the immunological endpoint per entryfor obtained for the antigen homologous to the munological endpoint values pervalues entry obtained the antigen homologous to the vaccine vaccine (x axis) against that obtained for a heterologous antigen (y axis)
Summary
Influenza A viruses pose a significant global burden on human and animal health. They are divided into subtypes based on the antigenic properties of their surface glycoproteins, the hemagglutinin (HA) and neuraminidase (NA). A pandemic can be sparked if such a zoonotic virus can transmit efficiently in the—mostly immunologically naïve—population These major threats to human health may have devastating socio-economic consequences, as observed currently with the COVID-19 pandemic, caused by a member of the coronavirus family. Viruses from different genetic and antigenic (sub)clades circulate concurrently, increasing the challenges linked to pandemic preparedness against. Viruses from the A/H5 GsGd lineage pose an additional challenge since inactivated A/H5 influenza virus vaccines generally have low immunogenicity in humans as compared to inactivated seasonal influenza virus vaccines [12]. Most of them are inactivated vaccines and based on old antigenic variants which might result in limited immunogenicity and cross-reactivity against currently circulating A/H5 GsGd viruses. We review the literature available on the breadth of antibody responses induced by A/H5 influenza virus vaccines in humans upon homologous and heterologous primeboost vaccinations to identify aspects correlating with high immunogenicity and crossreactivity, as measured by several immunological endpoints against the vaccine antigen and heterologous antigens
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