Immune Responses to Pandemic H1N1 Influenza Virus Infection in Pigs Vaccinated with a Conserved Hemagglutinin HA1 Peptide Adjuvanted with CAF®01 or CDA/αGalCerMPEG.

Sergi López-Serrano,Lorena Cordoba,Carlos A Guzmán,Edmond J Remarque,Ayub Darji,Joaquim Segalés,Mónica Pérez-Maillo,Dennis Christensen,Thomas Ebensen,Patricia Pleguezuelos

doi:10.3390/vaccines9070751

Abstract

This study aimed to evaluate the immune response and protection correlates against influenza virus (IV) infection in pigs vaccinated with the novel NG34 HA1 vaccine candidate adjuvanted with either CAF®01 or CDA/αGalCerMPEG (αGCM). Two groups of six pigs each were vaccinated intramuscularly twice with either NG34 + CAF®01 or NG34 + CDA/αGCM. As controls, groups of animals (n = 6 or 4) either non-vaccinated or vaccinated with human seasonal trivalent influenza vaccine or NG34 + Freund’s adjuvant were included in the study. All animal groups were challenged with the 2009 pandemic (pdm09) strain of H1N1 (total amount of 7 × 106 TCID50/mL) via intranasal and endotracheal routes 21 days after second vaccination. Reduced consolidated lung lesions were observed both on days three and seven post-challenge in the animals vaccinated with NG34 + CAF®01, whereas higher variability with relatively more severe lesions in pigs of the NG34 + CDA/αGCM group on day three post-infection. Among groups, animals vaccinated with NG34 + CDA/αGCM showed higher viral loads in the lung at seven days post infection whereas animals from NG34 + CAF®01 completely abolished virus from the lower respiratory tract. Similarly, higher IFNγ secretion and stronger IgG responses against the NG34 peptide in sera was observed in animals from the NG34 + CAF®01 group as compared to the NG34 + CDA/αGCM. NG34-vaccinated pigs with adjuvanted CAF®01 or CDA/αGCM combinations resulted in different immune responses as well as outcomes in pathology and viral shedding.

Highlights

Influenza is a contagious disease caused by Influenza viruses (IV) that mainly can affect birds, which represent the natural reservoir and mammals that act as natural hosts [1]
This study aimed to evaluate the immune response and protection correlates against influenza virus (IV) infection in pigs vaccinated with the novel NG34 Hemagglutinin 1 (HA1) vaccine candidate adjuvanted with either Cationic Adjuvant Formulation 01” (CAF®01) or cyclic dimeric adenosine monophosphate (CDA)/αGalCerMPEG
In the present study we examined the immune correlates that may define protection against IV infection in pigs immunized with the NG34 peptide adjuvanted with either a liposome based “Cationic Adjuvant Formulation 01” (CAF®01) or a combination of bis-(3,5)-cyclic dimeric adenosine monophosphate (CDA) and α-galactosylceramide methoxypolyethylene glycol

Summary

Introduction

Influenza is a contagious disease caused by Influenza viruses (IV) that mainly can affect birds, which represent the natural reservoir and mammals that act as natural hosts [1]. Vaccination is considered the most important and effective strategy to prevent and control IAV infection and disease in both animals and humans. Current strategies to combat IAV infection include vaccines that consist seasonal trivalent/quadrivalent Influenza Virus (IV) strains, based on inactivated virus or its corresponding hemagglutinins with or without additional adjuvants [5]. The immune responses triggered by these vaccines; these are strain specific and do not protect individuals against heterologous emerging strains, because of the characteristic mutating nature of IVs. Multivalent or universal vaccines, based on conserved antigen motifs from influenza virus, could be an attractive albeit challenging strategy to broadly prevent influenza virus infection and reduce the risk of influenza pandemics [6,7,8]. On the other hand, are often poor immunogens and may require additional adjuvants to induce the strong humoral and cellular immune responses needed to overcome IV infection [9]

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