BACKGROUND: The expression of Moloney murine leukemia virus (Mo-MLV) gag proteins is sufficient to generate retrovirus-like particles (retroVLPs) that can be used as antigen-display platforms by pseudotyping with heterologous envelope proteins or by insertion of epitopes in structural constituents. To circumvent the in vitro production of such retroVLPs, we used DNA plasmids generating recombinant retroVLPs (plasmo-retroVLPs) as immunogens. We previously demonstrated that plasmo-retroVLPs induce significantly better antigen-specific T cell responses and antiviral immune protection than plasmids bearing a single mutation preventing retroVLPs assembly. In the present study, we investigated the possibility of using such plasmo-retroVLPs in prime-boost immunization strategies for hepatitis C virus (HCV) vaccine development. METHODS: To define the best immunization regimen with plasmo-retroVLPs and serotype 5 recombinant adenovirus vectors (rAd5), we used standardized methodologies measuring immune responses to the GP(33-41) 'gold standard' antigen. The protective efficacy of these immunization schedules was also evaluated in mice after tumor challenge. We then applied the optimal prime-boost immunization strategy using vectors expressing HCV-E1/E2 envelope glycoproteins. RESULTS: Using vectors expressing the model antigen, we demonstrated that rAd5(GP33-41)/plasmo-retroVLP(GP33-41) regimen induced significantly higher cellular immune responses than plasmo-retroVLP(GP33-41)/rAd5(GP33-41). Consequently, HCV-specific plasmo-retroVLPs (plasmo-retroVLP(E1E2)) were used as boost in mice primed with rAd5(E1E2) and we observed that plasmo-retroVLP(E1E2) significantly increased E1/E2-specific interferon-gamma cellular responses and E2-specific antibody generation. By contrast, plasmids unable to form E1/E2-pseudotyped retroVLPs had no boosting effect, revealing the importance of presenting E1/E2 in a particulate form. CONCLUSIONS: Altogether, combining plasmo-retroVLPs that represent a new class of genetic vaccines in a heterologous prime-boost vaccination strategy appears to be a promising strategy for HCV vaccine development.
BACKGROUND: The expression of Moloney murine leukemia virus (Mo-MLV) gag proteins is sufficient to generate retrovirus-like particles (retroVLPs) that can be used as antigen-display platforms by pseudotyping with heterologous envelope proteins or by insertion of epitopes in structural constituents. To circumvent the in vitro production of such retroVLPs, we used DNA plasmids generating recombinant retroVLPs (plasmo-retroVLPs) as immunogens. We previously demonstrated that plasmo-retroVLPs induce significantly better antigen-specific T cell responses and antiviral immune protection than plasmids bearing a single mutation preventing retroVLPs assembly. In the present study, we investigated the possibility of using such plasmo-retroVLPs in prime-boost immunization strategies for hepatitis C virus (HCV) vaccine development. METHODS: To define the best immunization regimen with plasmo-retroVLPs and serotype 5 recombinant adenovirus vectors (rAd5), we used standardized methodologies measuring immune responses to the GP(33-41) 'gold standard' antigen. The protective efficacy of these immunization schedules was also evaluated in mice after tumor challenge. We then applied the optimal prime-boost immunization strategy using vectors expressing HCV-E1/E2 envelope glycoproteins. RESULTS: Using vectors expressing the model antigen, we demonstrated that rAd5(GP33-41)/plasmo-retroVLP(GP33-41) regimen induced significantly higher cellular immune responses than plasmo-retroVLP(GP33-41)/rAd5(GP33-41). Consequently, HCV-specific plasmo-retroVLPs (plasmo-retroVLP(E1E2)) were used as boost in mice primed with rAd5(E1E2) and we observed that plasmo-retroVLP(E1E2) significantly increased E1/E2-specific interferon-gamma cellular responses and E2-specific antibody generation. By contrast, plasmids unable to form E1/E2-pseudotyped retroVLPs had no boosting effect, revealing the importance of presenting E1/E2 in a particulate form. CONCLUSIONS: Altogether, combining plasmo-retroVLPs that represent a new class of genetic vaccines in a heterologous prime-boost vaccination strategy appears to be a promising strategy for HCV vaccine development.
Authors: Gaëlle Gottrand; Tristan Courau; Véronique Thomas-Vaslin; Nicolas Prevel; Thomas Vazquez; Maria Grazia Ruocco; Benedicte Lambrecht; Bertrand Bellier; Bruno M Colombo; David Klatzmann Journal: Immunology Date: 2015-10-28 Impact factor: 7.397
Authors: Matthias Kreppel; Ali-Farid Safi; Martin Scheer; Hans-Joachim Nickenig; Joachim Zöller; Simon Preuss; Moritz Meyer; Daniel Rothamel; Timo Dreiseidler Journal: Eur Arch Otorhinolaryngol Date: 2015-09-07 Impact factor: 2.503
Authors: Thomas Lener; Mario Gimona; Ludwig Aigner; Verena Börger; Edit Buzas; Giovanni Camussi; Nathalie Chaput; Devasis Chatterjee; Felipe A Court; Hernando A Del Portillo; Lorraine O'Driscoll; Stefano Fais; Juan M Falcon-Perez; Ursula Felderhoff-Mueser; Lorenzo Fraile; Yong Song Gho; André Görgens; Ramesh C Gupta; An Hendrix; Dirk M Hermann; Andrew F Hill; Fred Hochberg; Peter A Horn; Dominique de Kleijn; Lambros Kordelas; Boris W Kramer; Eva-Maria Krämer-Albers; Sandra Laner-Plamberger; Saara Laitinen; Tommaso Leonardi; Magdalena J Lorenowicz; Sai Kiang Lim; Jan Lötvall; Casey A Maguire; Antonio Marcilla; Irina Nazarenko; Takahiro Ochiya; Tushar Patel; Shona Pedersen; Gabriella Pocsfalvi; Stefano Pluchino; Peter Quesenberry; Ilona G Reischl; Francisco J Rivera; Ralf Sanzenbacher; Katharina Schallmoser; Ineke Slaper-Cortenbach; Dirk Strunk; Torsten Tonn; Pieter Vader; Bas W M van Balkom; Marca Wauben; Samir El Andaloussi; Clotilde Théry; Eva Rohde; Bernd Giebel Journal: J Extracell Vesicles Date: 2015-12-31
Authors: Hugo R Soares; Rute Castro; Hélio A Tomás; Manuel J T Carrondo; Paula M Alves; Ana S Coroadinha Journal: AMB Express Date: 2019-02-07 Impact factor: 3.298