Poxvirus and vaccines



Mariano Esteban

Group Leader



Research summary

The main objectives of our laboratory are geared toward understanding the molecular basis of the pathogenesis of infectious agents and their interaction with the host, as well as to use this knowledge in the development of vaccines that might be effective against diseases like AIDS, malaria and leishmaniasis. As a model system of an infectious agent and as a delivery vector for expression of genes of interest, we used vaccinia virus (VV), a member of the poxvirus family.



Asbach B, Kliche A, Köstler J, Perdiguero B, Esteban M, Jacobs BL, Montefiori DC, LaBranche CC, Yates NL, Tomaras GD, Ferrari G, Foulds KE, Roederer M, Landucci G, Forthal DN, Seaman MS, Hawkins N, Self SG, Sato A, Gottardo R, Phogat S, Tartaglia J, Barnett SW, Burke B, Cristillo AD, Weiss DE, Francis J, Galmin L, Ding S, Heeney JL, Pantaleo G, Wagner R. Potential To Streamline Heterologous DNA Prime and NYVAC/Protein Boost HIV Vaccine Regimens in Rhesus Macaques by Employing Improved Antigens. J Virol. 2016; 90: 4133-49

Di Pilato M, Mejías-Pérez E, Zonca M, Perdiguero B, Gómez CE, Trakala M, Nieto J, Nájera JL, S Sorzano CO, Combadière C, Pantaleo G, Planelles L, Esteban M. NFκB activation by modified vaccinia virus as a novel strategy to enhance neutrophil migration and HIV-specific T-cell responses. Proc Natl Acad Sci U S A. 2015; 112: E1333-42

Perdiguero B, Gómez CE, Cepeda V, Sánchez-Sampedro L, García-Arriaza J, Mejías-Pérez E, Jiménez V, Sánchez C, Sorzano CÓ, Oliveros JC, Delaloye J, Roger T, Calandra T, Asbach B, Wagner R, Kibler KV, Jacobs BL, Pantaleo G, Esteban M. Virological and Immunological Characterization of Novel NYVAC-Based HIV/AIDS Vaccine Candidates Expressing Clade C Trimeric Soluble gp140(ZM96) and Gag(ZM96)-Pol-Nef(CN54) as Virus-Like Particles. J Virol. 2015; 89: 970-88

García-Arriaza J, Perdiguero B, Heeney J, Seaman M, Montefiori DC, Labranche C, Yates NL, Shen X, Tomaras GD, Ferrari G, Foulds KE, McDermott A, Kao SF, Roederer M, Hawkins N, Self S, Yao J, Farrell P, Phogat S, Tartaglia J, Barnett SW, Burke B, Cristillo A, Weiss D, Lee C, Kibler K, Jacobs B, Asbach B, Wagner R, Ding S, Pantaleo G, Esteban M. Head-to-head comparison of poxvirus NYVAC and ALVAC vectors expressing identical HIV-1 clade C immunogens in prime/boost combination with Env protein in non-human primates. J Virol. 2015; 89: 8525-39

Gómez CE, Perdiguero B, García-Arriaza J, Cepeda V, Sánchez-Sorzano CÓ, Mothe B, Jiménez JL, Muñoz-Fernández MÁ, Gatell JM, López Bernaldo de Quirós JC, Brander C, García F, Esteban M. A Phase I Randomized Therapeutic MVA-B Vaccination Improves the Magnitude and Quality of the T Cell Immune Responses in HIV-1-Infected Subjects on HAART. PLoS One. 2015; 10: e0141456


Diapositiva3The main objectives of our laboratory are geared to understanding the molecular basis of the pathogenesis of infectious agents and their interaction with the host, and to use this knowledge to develop effective vaccines against human diseases like HIV/AIDS, hepatitis C, chikungunya, malaria, leishmaniasis, and prostate cancer. As a model system of an infectious agent and as a delivery vector to express genes of interest, we use vaccinia virus (VV), a member of the poxvirus family.

The research areas in our lab are a) vaccinia virus structure, b) the mechanism of interferon antiviral and antitumor action, c) virus-host cell interaction, and d) development of vaccines for prevalent human diseases.

Our main achievements in 2013-2014 include
1) The first therapeutic phase I clinical trial in Spain with the HIV/AIDS vaccine candidate MVA-B developed by our group, in HIV-infected individuals under HAART (highly active antiretroviral therapy). The results showed a good safety profile and immunogenicity, particularly for specific activation of CD4+ T cells and induction of anti-V1/V2 antibodies, a marker of protection. In addition, the vaccine induced a tendency to reduced viral load after antiretroviral interruption.

2) We developed a vaccine against chikungunya virus, an RNA virus that causes severe articular pains and is spreading worldwide via the tiger mosquito Aedes albopictus.

3) We developed vectors based on the attenuated VV strain NYVAC expressing HIV-1 clade C trimeric gp140 and Gag-Pol-Nef, which showed excellent immune behaviour in preclinical trials. These vectors are being tested for safety and immunogenicity in phase I clinical trials.

4) We genetically modified the poxvirus-based vaccine candidates MVA and NYVAC by selective deletion of viral immunomodulatory genes, and showed optimised immunological behaviour against HIV.

5) We identified a mechanism of HIV immune activation through NYVAC modulation of the functional switch in neutrophils.






Mariano Esteban Principal investigator
Beatriz Perdiguero Postdoctoral scientist
Lucas Sánchez Postdoctoral scientist
Ernesto Mejías Predoctoral scientist
Suresh Chithathur Predoctoral scientist
María Victoria Jiménez Technician
Cristina Sánchez Technician

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