Improvement of the Trivalent Inactivated Flu Vaccine Using PapMV Nanoparticles

Abstract

Commercial seasonal flu vaccines induce production of antibodies directed mostly towards hemaglutinin (HA). Because HA changes rapidly in the circulating virus, the protection remains partial. Several conserved viral proteins, e.g., nucleocapsid (NP) and matrix proteins (M1), are present in the vaccine, but are not immunogenic. To improve the protection provided by these vaccines, we used nanoparticles made of the coat protein of a plant virus (papaya mosaic virus; PapMV) as an adjuvant. Immunization of mice and ferrets with the adjuvanted formulation increased the magnitude and breadth of the humoral response to NP and to highly conserved regions of HA. They also triggered a cellular mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain (WSN/33). Thus, seasonal flu vaccine adjuvanted with PapMV nanoparticles can induce universal protection to influenza, which is a major advancement when facing a pandemic.

Nanoparticle Adjuvant Sensing by TLR7 Enhances CD8+ T Cell–Mediated Protection from Listeria Monocytogenes Infection

“…immunization, splenic DCs take up PapMV in vivo and acquire a mature phenotype (22). In addition, we recently showed that s.c (34). and intranasal (27) administration of PapMV leads to the production of proinflammatory cytokines and chemokines.…”

“…This is likely the result of the direct cross-linking of specific B cell receptors by repeated antigenic patterns found on the surface of PapMV nanoparticles, which could induce Ab production without help from CD4 + T cells. Although some studies have shown that Abs directed toward a vaccine platform can be detrimental to the effectiveness of a recall injection (41), the presence of high levels of Abs against PapMV does not affect the efficacy of a booster vaccination (19,27,34).…”

Crystal Structure of the Coat Protein of the Flexible Filamentous Papaya Mosaic Virus

“…We have previously shown that the PapMVCP and modified versions of the protein can be produced in bacteria where they self-assemble into nanoparticles in Escherichia coli that resemble the wild-type PapMV virus purified from infected plants. 20 This expression system was used for biochemical investigation of the PapMV CP and also for engineering chimeric recombinant nanoparticles that may be used as adjuvant 21,22 or as a vaccine platform. [23][24][25] PapMV nanoparticles appear to be perceived by the innate immune system as a pathogen-associated molecular pattern.…”

Development of a universal CTL-based vaccine for influenza

“…In humans, preceding titers of specific anti NP IgG can be boosted in only few cases in subjects immunized with conventional trivalent vaccines. 64 In a similar way, Savard et al 66 found that NP and M1 proteins present in split virion seasonal flu vaccine, are not immunogenic in immunized mice. However they showed that immunization of mice and ferrets with the same vaccine adjuvanted with papaya mosaic virus nanoparticles triggered a cell-mediated immune response to NP and M1, and long-lasting protection in animals challenged with a heterosubtypic influenza strain.…”