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Vaccine Detail

HIV priming with DNA vaccine expressing HIV gp160 protein and boosted with Ad5/35 vector expressing the same protein
Vaccine Information
  • Vaccine Name: HIV priming with DNA vaccine expressing HIV gp160 protein and boosted with Ad5/35 vector expressing the same protein
  • Target Pathogen: Human Immunodeficiency Virus
  • Target Disease: Acquired Immunodeficiency Syndrome (AIDS)
  • Vaccine Ontology ID: VO_0000789
  • Type: DNA vaccine
  • Antigen: HIV Env gp160 protein (Xin et al., 2005)
  • env gene engineering:
    • Type: Recombinant vector construction
    • Description: An Ad5/35 vector was used to express HIV Env gp160 protein (Ad5/35-HIV) (Xin et al., 2005).
    • Detailed Gene Information: Click Here.
  • env gene engineering:
    • Type: DNA vaccine construction
    • Description: The DNA vaccine contained env and rev from HIV-1 IIIB (Xin et al., 2005).
    • Detailed Gene Information: Click Here.
  • rev from HIV 1 gene engineering:
    • Type: DNA vaccine construction
    • Description: The DNA vaccine contained env and rev from HIV-1 IIIB (Xin et al., 2005).
    • Detailed Gene Information: Click Here.
  • DNA vaccine plasmid: Pcaggs DNA vaccine plasmid
  • Preparation: A replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35) was prepared and used to express HIV Env gp160 protein. The product is named Ad5/35-HIV (Xin et al., 2005).
  • Virulence: This novel Ad5/35 vector showed minimal hepatotoxicity after intramuscular administration with the novel Ad5/35 vector (Xin et al., 2005).
  • Description: Replication-defective Ad5 HIV recombinants and replication-defective MVA elicit potent CD8+ T-cell responses and provide a high degree of protection in NHPs. The Ad5 (subgroup C) has well-defined biological properties and has been widely used as a vector for gene therapy and vaccine. The replication-defective Ad5 vector can easily be produced in high titers and is highly effective in boosting HIV-specific immunity. However, this virus uses CAR as its primary attachment receptor, which confers tropism for liver parenchymal cells. This raises important safety concerns. Thus, a replication-defective chimeric Ad5 vector with Ad type 35 fiber (Ad5/35) has been developed, which not only induces strong antigen-specific humoral and cellular immune responses and exhibits minimal hepatotoxicity in both mice and NHPs, but is also significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector (Xin et al., 2005).
Host Response

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: 1011 vp of Ad5/35-HIV vector was injected i.m. into two rhesus monkeys (2 years old, male) at weeks 0 and 8 (Xin et al., 2005).
  • Immune Response: A detectable HIV-specific serum Ab response developed within 2 weeks of the first immunization. At 4 weeks post boosting, titers in excess of 1:50 000 were achieved. Similar results were observed in neutralizing Ab. A increase in the number of HIV-specific IFN-gamma-secreting T cells was also detected in the peripheral blood mononuclear cells (PBMCs). Boosting with Ad5/35-HIV vector further increased this T-cell response (Xin et al., 2005).
  • Side Effects: Liver infection with Ad5 vector was 20- to 40-fold stronger than that with Ad5/35 vector. Ad5-Luc vector was two- and four-fold higher, respectively, than that of the monkeys that received the Ad5/35-Luc vector. The Ad5/35 recombinants exhibits minimal hepatotoxicity in non-human primates but is also significantly less susceptible to the pre-existing Ad5 immunity than a comparable Ad5 vector (Xin et al., 2005).

Mouse Response

  • Vaccination Protocol: Mice were injected i.m. with Ad5-Luc or Ad5/35-Luc. Luciferase expression was monitored using an in vivo imaging system (IVIS). The expression of HIV gp160 was confirmed by Western blotting. Mice were immunized with Ad5/35-HIV vector, and the HIV-specific CMI was periodically monitored by the intracellular cytokine staining (ICS) assay (Xin et al., 2005).
  • Immune Response: The animals immunized with Ad5/35-HIV vector developed a high-titered anti-gp160 antibody (Ab) response. The magnitude of this response was not significantly altered by preimmunization with the DNA-HIV vaccine. DNA-HIV vaccination alone generated a low level of HIV-specific serum Ab. HIV-specific neutralizing Ab was only detectable in the Ad5/35-HIV vaccinated mice and DNA prime/Ad5/35-HIV boosted mice. HIV-specific cellular immune responses persisted through 7 months after final immunization (Xin et al., 2005).
  • Side Effects: The hepatotoxicity caused by the Ad5 vector was circumvented by the use of an Ad5/35 vector (Xin et al., 2005).
  • Challenge Protocol: Immunized mice were challenged with vPE16 2 weeks after final immunization. Vaccinated mice were challenged with vPE16 7 weeks after final immunization. The strain vPE16 is HIVBH8 gp160-expressing replication-competent vaccinia virus (WR strain, vPE16; HIVBH8 gp160 has 97.32% amino-acid homology with HIVIIIB gp160) (Xin et al., 2005).
  • Efficacy: The animals that were vaccinated with the Ad5/35 vector alone or in combination with the DNA-HIV vaccine were completely protected from infection; however, the DNA-HIV vaccination alone had little impact on the susceptibility to infection by vPE16. DNA-HIV vaccination by itself was not protective, but the combination of DNA-HIV priming and Ad5/35-HIV boosting yielded a prolonged and complete protection (Xin et al., 2005).
References
Xin et al., 2005: Xin KQ, Jounai N, Someya K, Honma K, Mizuguchi H, Naganawa S, Kitamura K, Hayakawa T, Saha S, Takeshita F, Okuda K, Honda M, Klinman DM, Okuda K. Prime-boost vaccination with plasmid DNA and a chimeric adenovirus type 5 vector with type 35 fiber induces protective immunity against HIV. Gene therapy. 2005 Dec; 12(24); 1769-77. [PubMed: 16079886].