المؤلفون: Martins, Mauricio A., Shin, Young C., Gonzalez-Nieto, Lucas, Domingues, Aline, Gutman, Martin J., Maxwell, Helen S., Castro, Iris, Magnani, Diogo M., Ricciardi, Michael, Pedreño-Lopez, Nuria, Bailey, Varian, Betancourt, Dillon, Altman, John D., Pauthner, Matthias, Burton, Dennis R., von Bredow, Benjamin, Evans, David T., Yuan, Maoli, Parks, Christopher L., Ejima, Keisuke

المصدر: PLoS Pathogens; 7/21/2017, Vol. 13 Issue 7, p1-32, 32p

مصطلحات موضوعية: SIMIAN immunodeficiency virus diseases, SIMIAN immunodeficiency virus diseases vaccines, GAG proteins, VIRAL vaccines, IMMUNOREGULATION, VIRAL replication, VACCINE effectiveness, IMMUNOLOGY

مستخلص: The ability to control lentivirus replication may be determined, in part, by the extent to which individual viral proteins are targeted by the immune system. Consequently, defining the antigens that elicit the most protective immune responses may facilitate the design of effective HIV-1 vaccines. Here we vaccinated four groups of rhesus macaques with a heterologous vector prime/boost/boost/boost (PBBB) regimen expressing the following simian immunodeficiency virus (SIV) genes: env, gag, vif, rev, tat, and nef (Group 1); env, vif, rev, tat, and nef (Group 2); gag, vif, rev, tat, and nef (Group 3); or vif, rev, tat, and nef (Group 4). Following repeated intrarectal challenges with a marginal dose of the neutralization-resistant SIVmac239 clone, vaccinees in Groups 1–3 became infected at similar rates compared to control animals. Unexpectedly, vaccinees in Group 4 became infected at a slower pace than the other animals, although this difference was not statistically significant. Group 1 exhibited the best post-acquisition virologic control of SIV infection, with significant reductions in both peak and chronic phase viremia. Indeed, 5/8 Group 1 vaccinees had viral loads of less than 2,000 vRNA copies/mL of plasma in the chronic phase. Vaccine regimens that did not contain gag (Group 2), env (Group 3), or both of these inserts (Group 4) were largely ineffective at decreasing viremia. Thus, vaccine-induced immune responses against both Gag and Env appeared to maximize control of immunodeficiency virus replication. Collectively, these findings are relevant for HIV-1 vaccine design as they provide additional insights into which of the lentiviral proteins might serve as the best vaccine immunogens. [ABSTRACT FROM AUTHOR]

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المؤلفون: Rabinovich, Svetlana, Powell, Rebecca L. R., Lindsay, Ross W. B., Yuan, Maoli, Carpov, Alexei, Wilson, Aaron, Lopez, Mary, Coleman, John W., Wagner, Denise, Sharma, Palka, Kemelman, Marina, Wright, Kevin J., Seabrook, John P., Arendt, Heather, Martinez, Jennifer, DeStefano, Joanne, Chiuchiolo, Maria J., Parks, Christopher L.

المصدر: PLoS ONE; Sep2014, Vol. 9 Issue 9, p1-17, 17p

مصطلحات موضوعية: VESICULAR stomatitis, CONFORMATIONAL analysis, HIV infections, LABORATORY mice, VIRAL replication, VACCINATION

مستخلص: Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by SIV challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying HIV immunogens must be considered. We have designed a replication-competent vesicular stomatitis virus (VSV) displaying immunogenic HIV-1 Env trimers and attenuating quantities of the native surface glycoprotein (G). The clade B Env immunogen is an Env-VSV G hybrid (EnvG) in which the transmembrane and cytoplasmic tail regions are derived from G. Relocation of the G gene to the 5′terminus of the genome and insertion of EnvG into the natural G position induced a ∼1 log reduction in surface G, significant growth attenuation compared to wild-type, and incorporation of abundant EnvG. Western blot analysis indicated that ∼75% of incorporated EnvG was a mature proteolytically processed form. Flow cytometry showed that surface EnvG bound various conformationally- and trimer-specific antibodies (Abs), and in-vitro growth assays on CD4+CCR5+ cells demonstrated EnvG functionality. Neither intranasal (IN) or intramuscular (IM) administration in mice induced any observable pathology and all regimens tested generated potent Env-specific ELISA titers of 10⁴–10⁵, with an IM VSV prime/IN VSV boost regimen eliciting the highest binding and neutralizing Ab titers. Significant quantities of Env-specific CD4+ T cells were also detected, which were augmented as much as 70-fold by priming with IM electroporated plasmids encoding EnvG and IL-12. These data suggest that our novel vector can achieve balanced safety and immunogenicity and should be considered as an HIV vaccine platform. [ABSTRACT FROM AUTHOR]

: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)