Vector replication and expression of HIV-1 antigens by the HIV/AIDS vaccine candidate MVA-B is not affected by HIV-1 protease inhibitors.
MVA-B is an attenuated poxvirus vector expressing human immunodeficiency virus type 1 Env, Gag, Pol, and Nef antigens from clade B, and is considered a promising HIV/AIDS vaccine candidate. Recently, a phase I clinical trial in human healthy volunteers has shown that MVA-B is safe and highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4(+) and CD8(+) T cell responses to HIV-1 antigens, with preference for effector memory T cells; and it also triggers the induction of specific antibodies to Env in most of the vaccines. While MVA recombinants expressing HIV-1 antigens are being used or plan to use in therapeutic clinical trials, little is known on the effect of HIV-1 highly active antiretroviral therapy in MVA life cycle. To define this role, here we have evaluated in established cell cultures and human dendritic cells to what extent different HIV-1 protease inhibitors affect virus replication and expression of HIV-1 antigens during MVA-B infection. The results obtained revealed that the most commonly used HIV-1 protease inhibitors (atazanavir, ritonavir, and lopinavir) had no effect on MVA-B virus growth kinetics, even at higher concentrations than those normally used on HAART. Furthermore, expression of gp120 and the fused Gag-Pol-Nef polyprotein in permissive and non-permissive cells infected with MVA-B were also not affected. These findings are relevant information for the therapeutic use of MVA-B as an HIV-1/AIDS vaccine.
Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
Juan
J
García-Arriaza
Pilar
P
Arnáez
José Luis
JL
Jiménez
Carmen E
CE
Gómez
María Ángeles
MÁ
Muñoz-Fernández
Mariano
M
Esteban
D016915:AIDS Vaccines / Q000276:immunology*; D000069446:Atazanavir Sulfate; D002460:Cell Line; D015488:HIV Antigens / Q000096:biosynthesis*; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D006801:Humans; D061466:Lopinavir / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009842:Oligopeptides / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D019438:Ritonavir / Q000494:pharmacology; D014616:Vaccinia virus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects*
D016915:AIDS Vaccines; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D019438:Ritonavir