First-in-Human Evaluation of the Safety and Immunogenicity of an Intranasally Administered Replication-Competent Sendai Virus-Vectored HIV Type 1 Gag Vaccine: Induction of Potent T-Cell or Antibody Responses in Prime-Boost Regimens

J Infect Dis. 2017 Jan 1;215(1):95-104. doi: 10.1093/infdis/jiw500. Epub 2016 Oct 17.


Background: We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine.

Methods: Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH).

Results: All vaccine regimens were well tolerated. Gag-specific IFN-γ enzyme-linked immunospot-determined response rates and geometric mean responses were higher (96% and 248 spot-forming units, respectively) in groups primed with SeV-Gag and boosted with Ad35-GRIN (SLA and SHA) than those after a single dose of Ad35-GRIN (56% and 54 spot-forming units, respectively) or SeV-Gag (55% and 59 spot-forming units, respectively); responses persisted for ≥8 months after completion of the prime-boost regimen. Functional CD8+ T-cell responses with greater breadth, magnitude, and frequency in a viral inhibition assay were also seen in the SLA and SHA groups after Ad35-GRIN boost, compared with those who received either vaccine alone. SeV-Gag did not boost T-cell counts in the ASH group. In contrast, the highest Gag-specific antibody titers were seen in the ASH group. Mucosal antibody responses were sporadic.

Conclusions: SeV-Gag primed functional, durable HIV-specific T-cell responses and boosted antibody responses. The prime-boost sequence appears to determine which arm of the immune response is stimulated.

Clinical trials registration: NCT01705990.

Keywords: HIV-1 vaccine; Sendai virus vector; adenovirus 35; immunogenicity; intranasal delivery; mucosal responses; prime-boost; replication competent.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects*
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology*
  • Administration, Intranasal
  • Adult
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Genes, Viral / immunology
  • Genetic Vectors
  • HIV Antibodies / blood
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • Humans
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunization, Secondary
  • Immunogenicity, Vaccine
  • Kenya
  • Male
  • Middle Aged
  • Rwanda
  • Sendai virus / genetics*
  • Sendai virus / immunology
  • Sendai virus / physiology
  • United Kingdom
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / adverse effects*
  • Vaccines, DNA / immunology*
  • Virus Replication


  • AIDS Vaccines
  • HIV Antibodies
  • Vaccines, DNA

Associated data