Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice Against Influenza A Virus

Overview

Journal Vaccines (Basel)

Date 2021 Nov 27

PMID 34835255

Citations 8

Authors

Kimberly Braz Gomes

Sucheta DSa

Grace Lovia Allotey-Babington

Sang-Moo Kang

Martin J DSouza

Affiliations

Soon will be listed here.

Abstract

In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel and Monophosphoryl Lipid-A (MPL-A), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4 T cells in the spleen and the lymph node and high levels of CD8 T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine.

Citing Articles

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References

Mosca F, Tritto E, Muzzi A, Monaci E, Bagnoli F, Iavarone C . Molecular and cellular signatures of human vaccine adjuvants. Proc Natl Acad Sci U S A. 2008; 105(30):10501-6. PMC: 2483233. DOI: 10.1073/pnas.0804699105. View

Mozdzanowska K, Maiese K, Furchner M, GERHARD W . Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology. 1999; 254(1):138-46. DOI: 10.1006/viro.1998.9534. View

Jalilian B, Christiansen S, Einarsson H, Pirozyan M, Petersen E, Vorup-Jensen T . Properties and prospects of adjuvants in influenza vaccination - messy precipitates or blessed opportunities?. Mol Cell Ther. 2015; 1:2. PMC: 4448954. View

Durando P, Iudici R, Alicino C, Alberti M, de Florentis D, Ansaldi F . Adjuvants and alternative routes of administration towards the development of the ideal influenza vaccine. Hum Vaccin. 2011; 7 Suppl:29-40. DOI: 10.4161/hv.7.0.14560. View

Marshall S, Sahm L, Moore A . The success of microneedle-mediated vaccine delivery into skin. Hum Vaccin Immunother. 2016; 12(11):2975-2983. PMC: 5137519. DOI: 10.1080/21645515.2016.1171440. View

Kreijtz J, Fouchier R, Rimmelzwaan G . Immune responses to influenza virus infection. Virus Res. 2011; 162(1-2):19-30. DOI: 10.1016/j.virusres.2011.09.022. View

Bachmann M, Jennings G . Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010; 10(11):787-96. DOI: 10.1038/nri2868. View

Manolova V, Flace A, Bauer M, Schwarz K, Saudan P, Bachmann M . Nanoparticles target distinct dendritic cell populations according to their size. Eur J Immunol. 2008; 38(5):1404-13. DOI: 10.1002/eji.200737984. View

Kovacsovics-Bankowski M, Clark K, Benacerraf B, Rock K . Efficient major histocompatibility complex class I presentation of exogenous antigen upon phagocytosis by macrophages. Proc Natl Acad Sci U S A. 1993; 90(11):4942-6. PMC: 46629. DOI: 10.1073/pnas.90.11.4942. View

10.

Giannini S, Hanon E, Moris P, Van Mechelen M, Morel S, Dessy F . Enhanced humoral and memory B cellular immunity using HPV16/18 L1 VLP vaccine formulated with the MPL/aluminium salt combination (AS04) compared to aluminium salt only. Vaccine. 2006; 24(33-34):5937-49. DOI: 10.1016/j.vaccine.2006.06.005. View

11.

Thomas P, Keating R, Hulse-Post D, Doherty P . Cell-mediated protection in influenza infection. Emerg Infect Dis. 2006; 12(1):48-54. PMC: 3291410. DOI: 10.3201/eid1201.051237. View

12.

Xiang S, Scholzen A, Minigo G, David C, Apostolopoulos V, Mottram P . Pathogen recognition and development of particulate vaccines: does size matter?. Methods. 2006; 40(1):1-9. DOI: 10.1016/j.ymeth.2006.05.016. View

13.

van de Ven K, de Heij F, van Dijken H, Ferreira J, de Jonge J . Systemic and respiratory T-cells induced by seasonal H1N1 influenza protect against pandemic H2N2 in ferrets. Commun Biol. 2020; 3(1):564. PMC: 7547016. DOI: 10.1038/s42003-020-01278-5. View

14.

Schotsaert M, Ysenbaert T, Neyt K, Ibanez L, Bogaert P, Schepens B . Natural and long-lasting cellular immune responses against influenza in the M2e-immune host. Mucosal Immunol. 2012; 6(2):276-87. DOI: 10.1038/mi.2012.69. View

15.

Tabata Y, Inoue Y, Ikada Y . Size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres. Vaccine. 1996; 14(17-18):1677-85. DOI: 10.1016/s0264-410x(96)00149-1. View

16.

Kim M, Song J, O E, Kwon Y, Lee Y, Compans R . Virus-like particles containing multiple M2 extracellular domains confer improved cross-protection against various subtypes of influenza virus. Mol Ther. 2012; 21(2):485-92. PMC: 3594028. DOI: 10.1038/mt.2012.246. View

17.

Bakkouri K, Descamps F, De Filette M, Smet A, Festjens E, Birkett A . Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol. 2010; 186(2):1022-31. DOI: 10.4049/jimmunol.0902147. View

18.

Kim M, Lee J, Choi H, Lee Y, Hwang H, Lee J . Microneedle patch delivery to the skin of virus-like particles containing heterologous M2e extracellular domains of influenza virus induces broad heterosubtypic cross-protection. J Control Release. 2015; 210:208-16. PMC: 4489561. DOI: 10.1016/j.jconrel.2015.05.278. View

19.

Didierlaurent A, Morel S, Lockman L, Giannini S, Bisteau M, Carlsen H . AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity. J Immunol. 2009; 183(10):6186-97. DOI: 10.4049/jimmunol.0901474. View

20.

Liu Z, Roche P . Macropinocytosis in phagocytes: regulation of MHC class-II-restricted antigen presentation in dendritic cells. Front Physiol. 2015; 6:1. PMC: 4311620. DOI: 10.3389/fphys.2015.00001. View