Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens

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• 作者：Pablo Penaloza MacMaster^a ; ^e ; Jennifer L. Shields^a ; Quazim A. Alayo^a ; Crystal Cabral^a ; Jessica Jimenez^a ; Jade Mondesir^a ; Abishek Chandrashekar^a ; Joseph M. Cabral^a ; Matthew Lim^a ; M. Justin Iampietro^a ; Nicholas M. Provine^a ; Christine A. Bricault^a ; Michael Seaman^a ; Klaus Orlinger^b ; Andreas Aspoeck^b ; Gerhard Fuhrmann^b ; Anders E. Lilja^b ; Thomas Monath^b ; Bastien Mangeat^c ; Daniel D. Pinschewer^c ; Dan H. Barouch^a ; ^d ; ^{dbarouch@bidmc.harvard.edu}
• 关键词：LCMV ; SIV ; NHP
• 刊名：Vaccine
• 出版年：2017
• 出版时间：3 January 2017
• 年：2017
• 卷：35
• 期：1
• 页码：1-9
• 全文大小：1574 K
• 卷排序：35

文摘

An important focus in vaccine research is the design of vaccine vectors with low seroprevalence and high immunogenicity. Replication-incompetent lymphocytic choriomeningitis virus (rLCMV) vectors do not elicit vector-neutralizing antibody responses, and homologous prime-boost regimens with rLCMV vectors induce boostable and protective T cell responses to model antigens in mice. However, cellular and humoral immune responses following homologous rLCMV vaccine regimens have not been rigorously evaluated in non-human primates (NHPs). To test whether rLCMV vectors constitute an effective vaccine platform in NHPs, we developed rLCMV vectors expressing SIVmac239 Env and Gag antigens and assessed their immunogenicity in mice and cynomolgus macaques. Immunization with rLCMV vaccine vectors expressing SIV Env and Gag was effective at generating SIV-specific T cell and antibody responses in both mice and NHPs. Epitope mapping using SIV Env in C57BL/6 mice demonstrated that rLCMV vectors induced sustained poly-functional responses to both dominant and subdominant epitopes. Our results suggest the potential of rLCMV vectors as vaccine candidates. Future SIV challenge experiments in rhesus macaques will be needed to assess immune protection by these vaccine vectors.