Prime-pull vaccination with a plant-derived virus-like particle influenza vaccine elicits a broad immune response and protects aged mice from death and frailty after challenge

Breanna Hodgins,Nathalie Landry,Brian J Ward,Stephane Pillet

doi:10.1186/s12979-019-0167-6

Abstract

BackgroundAdministered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge. Unlike split virus vaccines, VLPs can be administered by different routes including intranasally (IN). We evaluated novel vaccine strategies such as prime-pull (IM boosted by IN) and multi-modality vaccination (IM and IN given simultaneously). We wished to determine if these approaches would provide better quality protection in old mice after less severe (borderline-lethal) challenge (ie: immunogenicity, frailty and survival).ResultsSurvival rates were similar in all vaccinated groups. Antibody responses were modest in all groups but tended to be higher in VLP groups compared to inactivated influenza vaccine (IIV) recipients. All VLP groups had higher splenocyte T cell responses than the split virus group. Lung homogenate chemokine/cytokine levels and virus loads were lower in the VLP groups compared to IIV recipients 3 days after challenge (p < 0.05 for viral load vs all VLP groups combined). The VLP-vaccinated groups also had less weight loss and recovered more rapidly than the IIV recipients. There was limited evidence of an immunologic or survival advantage with IN delivery of the VLP vaccine.ConclusionCompared to IIV, the plant-derived VLP vaccine induced a broader immune response in aged mice (cellular and humoral) using either traditional (IM/IM) or novel schedules (multi-modality, prime-pull).

Highlights

Administered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge
The impact of influenza–associated morbidity is more difficult to quantify since even a short period of forced bed-rest, either at home or in hospital, can lead to major loss of muscle mass [5] and accumulation of other physiologic and mental deficits [6, 7]
Infection survival rates The viral challenge dose following the vaccination regimen as illustrated in Fig. 1 was intended to be severe but low enough to permit a good proportion of the animals to survive for determination of frailty after infection

Summary

Introduction

Administered intramuscularly (IM), plant-derived, virus-like-particle (VLP) vaccines based on the influenza hemagglutinin (HA) protein elicit both humoral and cellular responses that can protect aged mice from lethal challenge. After peripheral administration in mice, these plant-derived VLPs move rapidly to regional lymph nodes where they preferentially interact with B cells, NK cells and antigen-presenting cells (APC) [25] They interact directly with human immune cells including B cells and APC leading to activation [26], internalization [27] and presentation [28]. In clinical trials with healthy adults, the plantderived VLP vaccines elicit good antibody levels against seasonal strains and induce long-lived and poly-functional CD4+ T cell responses [29] The latter characteristic is of particular interest for older individuals since this population may be protected primarily by cellular immunity [31]

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Conclusion