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Vaccine. 2017 Jan 3;35(1):1-9. doi: 10.1016/j.vaccine.2016.11.063. Epub 2016 Nov 26.

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

Author information

1
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
3
Hookipa Biotech AG Helmut-Qualtinger-Gasse 2, 1030 Vienna, Austria.
4
Department of Biomedicine - Haus Petersplatz, Division of Experimental Virology, University of Basel, 4009 Basel, Switzerland.
5
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA; Ragon Institute of MGH, MIT, and Harvard, Boston, MA 02114, USA. Electronic address: dbarouch@bidmc.harvard.edu.

Abstract

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.

KEYWORDS:

LCMV; NHP; SIV

PMID:
27899229
PMCID:
PMC5147735
DOI:
10.1016/j.vaccine.2016.11.063
[Indexed for MEDLINE]
Free PMC Article

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