García-Arriaza J, Arnáez P, Jiménez JL, Gómez CE, Muñoz-Fernández MA, Esteban M.
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.