Abstract
In the search of strategies of presentation of heterologous antigens to elicit humoral or cellular immune responses that modulate and properly potentiate each type of response, researchers have been studying baculovirus (BV) as vaccine vectors with promising results. For some years, several research groups explored different antigen presentation approaches using the BV AcNPV by expressing polypeptides on the surface of budded virions or by de novo synthesis of heterologous antigens by transduction of mammalian cells. In the case of expression on the surface of budded virions, for example, researchers have expressed polypeptides in peplomers as GP64 glycoprotein fusions or distributed throughout the entire surface by fusions to portions of the G protein of vesicular stomatitis virus, VSV. Recently, our group developed the strategy of cross-presentation of antigens by fusions of GP64 to the capsid protein VP39 (capsid display) for the generation of cytotoxic responses. While the different strategies showed to be effective in raising immune responses, the individuality of each analysis makes difficult the comparison of the results. Here, by comparing the different strategies, we show that localization of the model antigen ovalbumin (OVA) strongly determined the quality and intensity of the adaptive response to the heterologous antigen. Furthermore, surface display favored humoral responses, whereas capsid display favored cytotoxic responses. Finally, capsid display showed a much more efficient strategy to activate CD8-mediated responses than transduction. The incorporation of adjuvants in baculovirus formulations dramatically diminished the immunostimulatory properties of baculovirus.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abe T, Matsuura Y (2010) Host innate immune responses induced by baculovirus in mammals. Curr Gene Ther 10:226–231
Abe T, Hemmi H, Miyamoto H, Moriishi K, Tamura S, Takaku H, Akira S, Matsuura Y (2005) Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus. J Virol 79:2847–2858
Argilaguet JM, Perez-Martin E, Lopez S, Goethe M, Escribano JM, Giesow K, Keil GM, Rodriguez F (2013) BacMam immunization partially protects pigs against sublethal challenge with African swine fever virus. Antivir Res 98:61–65. doi:10.1016/j.antiviral.2013.02.005
Boublik Y, Di Bonito P, Jones IM (1995) Eukaryotic virus display: engineering the major surface glycoprotein of the Autographa californica nuclear polyhedrosis virus (AcNPV) for the presentation of foreign proteins on the virus surface. Biotechnology (N Y) 13:1079–1084
Cao Y, Lu Z, Sun P, Fu Y, Tian F, Hao X, Bao H, Liu X, Liu Z (2011) A pseudotype baculovirus expressing the capsid protein of foot-and-mouth disease virus and a T-cell immunogen shows enhanced immunogenicity in mice. Virol J 8:77. doi:10.1186/1743-422X-8-77
Chapple SD, Jones IM (2002) Non-polar distribution of green fluorescent protein on the surface of Autographa californica nucleopolyhedrovirus using a heterologous membrane anchor. J Biotechnol 95:269–275
Fang R, Feng H, Nie H, Wang L, Tu P, Song Q, Zhou Y, Zhao J (2010) Construction and immunogenicity of pseudotype baculovirus expressing Toxoplasma gondii SAG1 protein in BALB/c mice model. Vaccine 28:1803–1807. doi:10.1016/j.vaccine.2009.12.005
Grabherr R, Ernst W, Oker-Blom C, Jones I (2001) Developments in the use of baculoviruses for the surface display of complex eukaryotic proteins. Trends Biotechnol 19:231–236
Hopkins R, Esposito D (2009) A rapid method for titrating baculovirus stocks using the Sf-9 easy titer cell line. BioTechniques 47:785–788. doi:10.2144/000113238
Ikawa M, Kominami K, Yoshimura Y, Tanaka K, Nishimune Y, Okabe M (1995) A rapid and non-invasive selection of transgenic embryos before implantation using green fluorescent protein (GFP). FEBS Lett 375:125–128
Iyori M, Nakaya H, Inagaki K, Pichyangkul S, Yamamoto DS, Kawasaki M, Kwak K, Mizukoshi M, Goto Y, Matsuoka H, Matsumoto M, Yoshida S (2013) Protective efficacy of baculovirus dual expression system vaccine expressing Plasmodium falciparum circumsporozoite protein. PLoS One 8:e70819. doi:10.1371/journal.pone.0070819
Kost TA, Condreay JP (2002) Recombinant baculoviruses as mammalian cell gene-delivery vectors. Trends Biotechnol 20:173–180
Kukkonen SP, Airenne KJ, Marjomaki V, Laitinen OH, Lehtolainen P, Kankaanpaa P, Mahonen AJ, Raty JK, Nordlund HR, Oker-Blom C, Kulomaa MS, Yla-Herttuala S (2003) Baculovirus capsid display: a novel tool for transduction imaging. Mol Ther 8:853–862
Lin SY, Chung YC, Hu YC (2014) Update on baculovirus as an expression and/or delivery vehicle for vaccine antigens. Expert Rev Vaccines 13:1501–1521. doi:10.1586/14760584.2014.951637
Mlambo G, Kumar N, Yoshida S (2010) Functional immunogenicity of baculovirus expressing Pfs25, a human malaria transmission-blocking vaccine candidate antigen. Vaccine 28:7025–7029. doi:10.1016/j.vaccine.2010.08.022
Molinari P, Crespo MI, Gravisaco MJ, Taboga O, Moron G (2011) Baculovirus capsid display potentiates OVA cytotoxic and innate immune responses. PLoS One 6:e24108. doi:10.1371/journal.pone.0024108
Moron G, Dadaglio G, Leclerc C (2004) New tools for antigen delivery to the MHC class I pathway. Trends Immunol 25:92–97. doi:10.1016/j.it.2003.11.008
Peralta A, Molinari P, Conte-Grand D, Calamante G, Taboga O (2007) A chimeric baculovirus displaying bovine herpesvirus-1 (BHV-1) glycoprotein D on its surface and their immunological properties. Appl Microbiol Biotechnol 75:407–414
Prabakaran M, Meng T, He F, Yunrui T, Qiang J, Lin RT, Kwang J (2011) Subcutaneous immunization with baculovirus surface-displayed hemagglutinin of pandemic H1N1 Influenza A virus induces protective immunity in mice. Clin Vaccine Immunol 18:1582–1585. doi:10.1128/CVI.05114-11
Rodrigo WW, Block OK, Lane C, Sukupolvi-Petty S, Goncalvez AP, Johnson S, Diamond MS, Lai CJ, Rose RC, Jin X, Schlesinger JJ (2009) Dengue virus neutralization is modulated by IgG antibody subclass and Fcgamma receptor subtype. Virology 394:175–182. doi:10.1016/j.virol.2009.09.024
Rohrmann GF (2013) Baculovirus molecular biology. 3rd edn., Bethesda (MD)
Thiele F, Tao S, Zhang Y, Muschaweckh A, Zollmann T, Protzer U, Abele R, Drexler I (2015) Modified vaccinia virus Ankara-infected dendritic cells present CD4+ T-cell epitopes by endogenous major histocompatibility complex class II presentation pathways. J Virol 89:2698–2709. doi:10.1128/JVI.03244-14
Xu XG, Wang ZS, Zhang Q, Li ZC, Zhao HN, Li W, Tong DW, Liu HJ (2011) Baculovirus surface display of E envelope glycoprotein of Japanese encephalitis virus and its immunogenicity of the displayed proteins in mouse and swine models. Vaccine 29:636–643. doi:10.1016/j.vaccine.2010.11.045
Yoshida S, Araki H, Yokomine T (2010) Baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice. Infect Immun 78:595–602. doi:10.1128/IAI.00877-09
Yuseff MI, Pierobon P, Reversat A, Lennon-Dumenil AM (2013) How B cells capture, process and present antigens: a crucial role for cell polarity. Nat Rev Immunol 13:475–486. doi:10.1038/nri3469
Acknowledgements
We acknowledge Mr. Silvio Diaz (INTA) for his help with mice experiments and Dr. María José Gravisaco for the assistance with the flow cytometer. We also acknowledge Dr. Julia Sabio y García for English language editing.
Funding
This work was supported by the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (grant number PICT 2012-395) and the Instituto Nacional de Tecnología Agropecuaria (INTA) (grant number PNBIO 1131032).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
This article does not contain studies with human participants or animals performed by any of authors.
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Eugenia Tavarone and Guido Nicolás Molina contributed equally as first authors. Paula Molinari and Oscar Taboga contributed equally as last authors.
Rights and permissions
About this article
Cite this article
Tavarone, E., Molina, G.N., Amalfi, S. et al. The localization of a heterologous displayed antigen in the baculovirus-budded virion determines the type and strength of induced adaptive immune response. Appl Microbiol Biotechnol 101, 4175–4184 (2017). https://doi.org/10.1007/s00253-017-8183-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-017-8183-y