A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Pillet, Stéphane; Aubin, Éric; Trépanier, Sonia; Bussière, Diane; Dargis, Michèle; Poulin, Jean-François; Yassine‐Diab, Bader; Ward, Brian J.; Landry, Nathalie

doi:10.1016/j.clim.2016.03.008

Cited by 122 publications

(107 citation statements)

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“…For instance, we have recently shown that these VLPs rapidly access draining lymph nodes (29), where they associate with and activate immune cells, including B cells, macrophages, and dendritic cells (30). Furthermore, these vaccines elicit balanced humoral and cellular responses in both preclinical (young mice and ferrets) and clinical studies in healthy young adults (10)(11)(12)31). The current work confirmed the earlier observation of balanced humoral and cellular responses following plant-made VLP vaccination in the young mice and extended these findings to much older animals.…”

Section: Discussionmentioning

confidence: 99%

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A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Hodgins

Yam

Winter

et al. 2017

Clin Vaccine Immunol

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Virus-like-particle (VLP) influenza vaccines can be given intramuscularly (i.m.) or intranasally (i.n.) and may have advantages over split-virion formulations in the elderly. We tested a plant-made VLP vaccine candidate bearing the viral hemagglutinin (HA) delivered either i.m. or i.n. in young and aged mice. Young adult (5-to 8-week-old) and aged (16-to 20-month-old) female BALB/c mice received a single 3-g dose based on the HA (A/California/07/2009 H1N1) content of a plant-made H1-VLP (i.m. or i.n.) split-virion vaccine (i.m.) or were left naive. After vaccination, humoral and splenocyte responses were assessed, and some mice were challenged. Both VLP and split vaccines given i.m. protected 100% of the young animals, but the VLP group lost the least weight and had stronger humoral and cellular responses. Compared to split-vaccine recipients, aged animals vaccinated i.m. with VLP were more likely to survive challenge (80% versus 60%). The lung viral load postchallenge was lowest in the VLP i.m. groups. Mice vaccinated with VLP i.n. had little detectable immune response, but survival was significantly increased. In both age groups, i.m. administration of the H1-VLP vaccine elicited more balanced humoral and cellular responses and provided better protection from homologous challenge than the splitvirion vaccine.KEYWORDS aged-mouse model, influenza, virus-like particles (VLPs), plant-made vaccines A ccording to the World Health Organization, influenza epidemics account for 250,000 to 500,000 deaths worldwide every year (http://www.who.int/mediacentre/factsheets/ fs211/en/). Although vaccines are widely recommended to protect against influenza, the elderly often respond poorly, in part due to prior experience with influenza virus antigens (Ag) (1), but also as a result of immunosenescence (2). The latter affects both innate and adaptive immune responses and has broad implications for both natural infection and vaccination (1, 2).Influenza vaccines for adults are administered by either intramuscular (i.m.) or intradermal injection of detergent-split virions at a fixed dose of 15 g hemagglutinin (HA)/strain (3). These vaccines typically elicit strong antibody responses in healthy young adults and achieve vaccine efficacy (VE) that varies between strains and years but averages 50 to 60% (4). These formulations work less well in the elderly (5

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Section: Discussionmentioning

confidence: 99%

“…and intranasal (i.n.) delivery (8)(9)(10)(11). These vaccines appear to elicit both strong antibody responses and long-lived and polyfunctional CD4 ϩ T cell responses (12).…”

mentioning

confidence: 99%

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Hodgins

Yam

Winter

et al. 2017

Clin Vaccine Immunol

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“…Their lead vaccine candidate, plant-derived influenza virus haemagglutinin (HA) virus-like particles, is currently being evaluated in phase 3 efficacy trials which, if successful, should lead to FDA approval by 2020. At the time of writing, influenza HA remains the only viral glycoprotein expressed in plants that has been evaluated in human trials (Pillet et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Production of complex viral glycoproteins in plants as vaccine immunogens

Margolin

Chapman

Williamson

et al. 2018

Plant Biotechnology Journal

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SummaryPlant molecular farming offers a cost‐effective and scalable approach to the expression of recombinant proteins which has been proposed as an alternative to conventional production platforms for developing countries. In recent years, numerous proofs of concept have established that plants can produce biologically active recombinant proteins and immunologically relevant vaccine antigens that are comparable to those made in conventional expression systems. Driving many of these advances is the remarkable plasticity of the plant proteome which enables extensive engineering of the host cell, as well as the development of improved expression vectors facilitating higher levels of protein production. To date, the only plant‐derived viral glycoprotein to be tested in humans is the influenza haemagglutinin which expresses at ~50 mg/kg. However, many other viral glycoproteins that have potential as vaccine immunogens only accumulate at low levels in planta. A critical consideration for the production of many of these proteins in heterologous expression systems is the complexity of post‐translational modifications, such as control of folding, glycosylation and disulphide bridging, which is required to reproduce the native glycoprotein structure. In this review, we will address potential shortcomings of plant expression systems and discuss strategies to optimally exploit the technology for the production of immunologically relevant and structurally authentic glycoproteins for use as vaccine immunogens.

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“…Plants possess the eukaryotic post-translational protein modification machinery broadly similar to that of mammals, do not harbor human pathogens, and can be rapidly scaled up as economic biomass generator. The plant-produced recombinant HA is in clinical study [17].…”

Section: Vaccine Production Technologiesmentioning

confidence: 99%

Current and Next Generation Vaccines Against Influenza

Kaminaka¹

2018

IJPC

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A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

Cited by 122 publications

References 71 publications

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

A Single Intramuscular Dose of a Plant-Made Virus-Like Particle Vaccine Elicits a Balanced Humoral and Cellular Response and Protects Young and Aged Mice from Influenza H1N1 Virus Challenge despite a Modest/Absent Humoral Response

Production of complex viral glycoproteins in plants as vaccine immunogens

Current and Next Generation Vaccines Against Influenza

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