Administration of Multivalent Influenza Virus Recombinant Hemagglutinin Vaccine in Combination-Adjuvant Elicits Broad Reactivity Beyond the Vaccine Components.

Jenny E Hernandez-Davies,Egest James Pone,Erwin Strahsburger,D Huw Davies,Algimantas Jasinskas,Aarti Jain,Shirin Strohmeier,Rie Nakajima,Florian Krammer,Sharon Jan,Jiin Felgner,Philip L Felgner

doi:10.3389/fimmu.2021.692151

Jenny E Hernandez-Davies, Egest James Pone + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2021.692151

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Abstract

Combining variant antigens into a multivalent vaccine is a traditional approach used to provide broad coverage against antigenically variable pathogens, such as polio, human papilloma and influenza viruses. However, strategies for increasing the breadth of antibody coverage beyond the vaccine are not well understood, but may provide more anticipatory protection. Influenza virus hemagglutinin (HA) is a prototypic variant antigen. Vaccines that induce HA-specific neutralizing antibodies lose efficacy as amino acid substitutions accumulate in neutralizing epitopes during influenza virus evolution. Here we studied the effect of a potent combination adjuvant (CpG/MPLA/squalene-in-water emulsion) on the breadth and maturation of the antibody response to a representative variant of HA subtypes H1, H5 and H7. Using HA protein microarrays and antigen-specific B cell labelling, we show when administered individually, each HA elicits a cross-reactive antibody profile for multiple variants within the same subtype and other closely-related subtypes (homosubtypic and heterosubtypic cross-reactivity, respectively). Despite a capacity for each subtype to induce heterosubtypic cross-reactivity, broader coverage was elicited by simply combining the subtypes into a multivalent vaccine. Importantly, multiplexing did not compromise antibody avidity or affinity maturation to the individual HA constituents. The use of adjuvants to increase the breadth of antibody coverage beyond the vaccine antigens may help future-proof vaccines against newly-emerging variants.

Highlights

Vaccines save millions of lives annually and represent one of the most cost-effective medical interventions for controlling infectious disease and the threat from pandemics
Reassortant influenza virus A/California/07/2009 (H1N1) x A/ Puerto Rico/8/1934 was obtained from BEI Resources (Manassas, VA; catalog #NR-44004), and A/Vietnam/1194/ 2004 (H5N1) x A/Puerto Rico/8/1934 and A/Shanghai/2/2013 x A/Puerto Rico/8/1934 were obtained from the National Institute for Biological Standards & Controls (NIBSC, South Mimms, UK; catalog #s NIBRG-14 and NIBRG-267, respectively)
A major aim of this study was to evaluate the breadth of the antibody response produced by an adjuvanted variant antigen vaccine

Summary

Introduction

Vaccines save millions of lives annually and represent one of the most cost-effective medical interventions for controlling infectious disease and the threat from pandemics. Despite the success of vaccination, achieving protection against rapidly evolving pathogens remains a challenge. This may be overcome by a vaccine that elicits cross-reactivity between variants, or by a multivalent approach that elicits multiple specific responses. Seasonal influenza results in 290,000-650,000 million deaths annually from respiratory disease [9]. Seasonal influenza is typically caused by type A and B influenza viruses. These are RNA viruses that possess an RNA-dependent RNA polymerase that is error-prone and lacks proof-reading function. Influenza B viruses do not exhibit the same strain diversity as type A and are found mainly in human hosts, and rarely, as a reverse zoonosis in seals [10]

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