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Vaccine Comparison

CVB4/p24(73(3)) DNA vaccine expressing multiple HIV epitopes Gag-VRPs gp120 recominant with GMDP adjuvant gp120 recominant with MDP adjuvant gp140, Gag and Tat Protein Vaccine with MF59 HIV priming with DNA vaccine expressing HIV gp160 protein and boosted with Ad5/35 vector expressing the same protein HIV recombinant gp160 Protein Vaccine Inactivated HIV-2 Vaccine with PMMA L. T -HIV-1 Gag MVA expressing HIV Gag, Pol and Env proteins Recombinant HIV gp120 with adjuvant NanoEmulsion rgp120 HIV Vaccine with immunoliposomes V3 VLPs with Gamma inulin adjuvant YF17D- HIV-1 p24
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004719
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • Preparation: A live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) (Gu et al., 2010).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0000817
  • Type: DNA vaccine
  • Antigen: The antigens are named MultiHIV-A (based on the subtype A consensus sequence), MultiHIV-B (subtype B consensus sequence), MultiHIV-C, and MultiHIV-FGH (based on ancestral sequence for subtypes F, G, and H). The MultiHIV DNAs encode polypeptides consisting of a fusion of the full-length regulatory proteins Rev, Nef and Tat as well structural proteins p17 and p24 (Malm et al., 2005).
  • rev from HIV 1 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Nef gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Tat gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Gag from HIV 1 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • env gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • pol gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: Auxo-GTU vector system (Malm et al., 2005)
  • Preparation: A vaccine platform was constructed with an HIV-1 subtype B DNA immunogen expressing full-length consensus sequences from HIV-1 rev, nef, tat, and gag with additional cellular epitope clusters from the env and pol regions. Furthermore, this platform has been extended to three additional plasmids expressing the same immunogens but originating from subtypes A or C consensus or FGH ancestral sequences (Malm et al., 2005).
  • Description: A significant limitation for HIV vaccine development is that there are no small animals in which actual productive HIV-1 infection can be established. DNA immunization with candidate vaccines comprising multiple genes of clades A, B, C, F, G, and H create strong cellular responses in BALB/c mice, especially after gene gun immunization (Malm et al., 2005).
  • Vaccine Ontology ID: VO_0000822
  • Antigen: HIV matrix-capsid portion of Gag, envelope gp160, secreted gp140, cloned SIVsm H-4i, SIVsm E660 (Davis et al., 2002)
  • Vector: VEE replicon particles (VRPs)
  • Preparation: Gag-VRPs is a cocktail vaccine of V3014-packaged VRPs expressing the SIVsm H-4i nonmyristylated matrix-capsid region, full-length gp160, and a secreted form of gp160 (gp140). Structural proteins for packaging of replicon RNA into VRPs are expressed from separate helper RNAs. VRPs expressing either the matrix-capsid portion of Gag, the full-length envelope gp160, or the secreted gp140 of cloned SIVsm H-4i were mixed in a cocktail and used to immunize macaques (Davis et al., 2002).
  • Vaccine Ontology ID: VO_0004233
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant HIV gp120 derived from CHO cells (Bomford et al., 1992).
  • Adjuvant: GMDP
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004234
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant HIV gp120 derived from CHO cells (Bomford et al., 1992).
  • Adjuvant: muramyl dipeptide
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004238
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: gp140, Gag and Tat recombinant proteins (Bråve et al., 2007).
  • Adjuvant: MF59
  • Immunization Route: Intramuscular injection (i.m.)
  • 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.
  • Vector: pCAGGS and a replication-defective chimeric Ad5 vector with the Ad35 fiber (Ad5/35)
  • 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).
  • Vaccine Ontology ID: VO_0004242
  • Type: Inactivated or "killed" vaccine
  • Status: Research
  • Adjuvant: PMMA
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004629
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • Gag from HIV 1 gene engineering:
    • Type: Recombinant vector construction
    • Description: A non-pathogenic Leishmania tarentolae was used to express full-length HIV-1 Gag protein (Breton et al., 2007).
    • Detailed Gene Information: Click Here.
  • Vector: (Breton et al., 2007)
  • Preparation: A non-pathogenic protozoan parasitic vector, Leishmania tarentolae, which shares common target cells with HIV-1, was used to express full-length HIV-1 Gag protein (Breton et al., 2007).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0000824
  • Type: Recombinant vector vaccine
  • Antigen: HIV Gag, Pol, and Env proteins (Liu et al., 2006)
  • Vector: modified vaccinia Ankara (MVA)
  • Preparation: An rMVA vaccine that expresses HIV Gag, Pol, and Env proteins was constructed (Liu et al., 2006).
  • Vaccine Ontology ID: VO_0000819
  • Type: Subunit vaccine
  • Antigen: HIV glycoprotein 120, which has a role in facilitating coreceptor interaction and in mediating virus binding to cellular CD4 (Bielinska et al., 2008).
  • Adjuvant: nanoemulsion vaccine adjuvant
    • VO ID: VO_0001319
    • Description: An oil-in-water nanoemulsion (NE) was used as the mucosal adjuvant for this vaccine (Bielinska et al., 2008).
  • Preparation: The gp120 and NE vaccines were prepared by mixing NE with gp120 protein solution, using pyrogen-free saline as a diluent (Bielinska et al., 2008).
  • Vaccine Ontology ID: VO_0004264
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: rgp120 (Ozpolat et al., 1998).
  • Adjuvant: immunoliposomes containing antibodies to costimulatory molecules
  • Immunization Route: subcutaneous injection
  • Vaccine Ontology ID: VO_0004232
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: gp120 V3 loop (Harris et al., 1996).
  • Adjuvant: gamma Inulin vaccine adjuvant
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004690
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Mouse
  • Preparation: HIV-1 p24 (clade B consensus), was inserted near the 5' end of YF17D, in frame and upstream of the polyprotein (YF-5'/p24) (Franco et al., 2010).
  • Immunization Route: Intramuscular injection (i.m.)
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Vaccination Protocol: Immunization was by intraperitoneal (IP) injection or by oral gavage. Mice were immunized with either CVB4/p24(733) or the parental CVB4. PBS-treated mice served as controls (Gu et al., 2010).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Mice immunized with the avirulent CVB4 variant are protected when subsequently challenged with a virulent variant (Gu et al., 2010).
  • Efficacy: Results showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice (Gu et al., 2010).

Mouse Response

  • Host Strain: C57BL/6, BALB/c
  • Vaccination Protocol: C57BL/6 mice were divided into groups g.g. immunized or i.m. inoculated. Mice were bled 2 weeks after the last immunization, and individual blood and spleen samples were collected post-challenge and used fresh in ELISPOT assays (Malm et al., 2005).
    BALB/c were immunized by MultiHIV/MultiClade DNA. Initially the immune response was evaluated after 3 immunizations by g.g. Equal amounts of clade A, B, C, and FGH MultiHIV plasmids were mixed together and coated onto the gold particles to construct the subtype cocktail MultiHIV DNA immunogen (MultiHIVmix). Mice were sacrificed 10 days after the last immunization and individual spleens were collected and the cells preserved at –70°C until used. In a second set of experiments a short-term immunization schedule was used to address three different administration routes; g.g., i.m., and i.d. Mice were immunized 3 times with MultiHIVmix DNA (Malm et al., 2005).
  • Immune Response: Though the immune response detected was quite low, the majority of g.g. immunized animals responded with specific IFN production. Interestingly, the gag specific response in the same gene gun immunized animals was weaker than the envelope responses and also drastically weaker than the responses seen before the experimental challenge (Malm et al., 2005). The CTL response, following i.d. injection, was detected five weeks after the first immunization and persisted up to 12 weeks later. In contrast, i.m. immunization induced detectable IFNy only at week 17 (Malm et al., 2005).
  • Side Effects: no side effects occurred (Malm et al., 2005)
  • Challenge Protocol: C57BL/6 mice transgenic for HLA-A201 were given an experimental challenge after a short-term immunization schedule. Amphotropic murine leukemia virus was used to prepare pseudovirus with HIV-1 isolate. Challenged animals were given i.p. injections of sHIV-1/MuLV infected cells (Malm et al., 2005).
  • Efficacy: The vaccine-induced immunity has in vivo efficacy. Here a mouse model showed that the HIV-1 GTU-MultiHIVmix vaccine induces virus-specific CD8 T cellular immunity and protects against experimental HIV-1 challenge (Malm et al., 2005).
  • Description: The cocktail of MultiHIV protected 19/24 animals against an experimental HIV-1 challenge. This experiment also demonstrates cross-clade protection, as the subtypes A and B viruses used for challenge were derived from different subtypes than the sequences found in the clade A or B specific MultiHIV constructs. Furthermore, it demonstrates that consensus approach used in Multi-HIVmix vaccine is functional and causes protection against naturally occurring isolates. Gene gun immunization was superior to intramuscular immunization in terms of both the T cell immunity induced, as well as higher frequency of protection. Data generated in this work support the hypothesis that DNA representing several HIV-1 subtypes and several genes are immunogenic and protective (Malm et al., 2005).
  • Host Ifng (Interferon gamma) response
    • Description: IFN-gamma levels in mice immunized by gene gun or intramuscular delivery with HIV-1 subtype B DNA immunogen showed strong up regulation in response to an H-2d restricted gag peptide (AMQMLKETI) and even stronger up-regulation in response to an env epitope (RGPGRAFVTI) (Malm et al., 2005).
    • Detailed Gene Information: Click Here.

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: VRPs with wild-type glycoprotein spikes were inoculated into the footpads of mice (Davis et al., 2002).
  • Persistence: At 11 months post-boosting with the downstream vector, serum antibody levels against HIV MA/CA were undiminished, and MA/CA specific CTLp were detectable in all mice tested. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins (Caley et al., 1999).
  • Immune Response: In BALB/c mice, the two vectors elicited cellular immune responses to MA/CA as determined by bulk CTL assays and precursor frequency analysis, but the humoral response induced by the downstream vector was significantly stronger. These findings suggest that VEE vectors can be optimized to elicit strong, balanced and long-lived immune responses to foreign viral proteins (Caley et al., 1999).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were subcutaneously immunized with antigen and adjuvant (Bomford et al., 1992).
  • Immune Response: Mice immunized with gp120 and GMDP in combination with pluronic emulsion resulted in a secondary antibody response (Bomford et al., 1992).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were subcutaneously immunized with antigen and adjuvant (Bomford et al., 1992).
  • Immune Response: Mice immunized with gp120 adjuvanted with MPD plus pleuronic emulsion resulted in a secondary antibody response (Bomford et al., 1992).

Mouse Response

  • Host Strain: C57Bl/6
  • Vaccination Protocol: The protein vaccine component consisted of 20 μg ro-gp140 delivered in the right tibialis muscle and 20 μg rGag and 5 μg rTat delivered in the left tibialis muscle. The proteins were formulated in 50% MF59 solution. Mock treatment consisted of MF59 adjuvant alone or empty DNA plasmid alone (Bråve et al., 2007).
  • Challenge Protocol: Briefly, 3 weeks after the final immunization (week 12), the animals were injected intraperitoneally with 1 million syngeneic splenocytes infected with HIV-1/MuLV of subtype B (LAI) (Bråve et al., 2007).
  • Efficacy: 83% of mice were tested negative for HIV-1 after challenge (Bråve et al., 2007).

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).

Mouse Response

  • Vaccination Protocol: The potency of the vaccine was determined by injecting mice with serial dilutions of gp160 alone or adjuvanted with different formulations. Groups of 10 mice were injected subcutaneously with 1 ml of fourfold dilutions of the test substance. A total of 50 mice were injected in each test (Barrett et al., 1989).
  • Immune Response: The highest potency in mice was obtained using a preparation with 0.2% Al(OH)3 and 0.25% deoxycholate (Barrett et al., 1989).

Mouse Response

  • Host Strain: NMRI
  • Vaccination Protocol: Mice received 0.5 ml of the specified vaccine preparations subcutaneously under the abdominal skin on day 0 (Stieneker et al., 1991).
  • Immune Response: Mice immunized with PMMA adjuvant had higher antibody counts than mice immunized with an alum adjuvant (Stieneker et al., 1991).

Mouse Response

  • Host Strain: Balb/c
  • Vaccine Immune Response Type: VO_0003057
  • Immune Response: Immunization of BALB/c mice with recombinant L. tarentolae led to the expansion of HIV-1 Gag-specific T cells and stimulated CD8(+) T cells to produce gamma interferon in response to specific viral Gag epitopes. A booster immunization with recombinant L. tarentolae elicited effector memory HIV-1 Gag-specific CD4(+) T lymphocytes and increased antibody titres against HIV-1 Gag (Breton et al., 2007).
  • Efficacy: Immunization of human tonsillar tissue cultured ex vivo with Gag-expressing L. tarentolae vaccine vector elicited a 75% decrease in virus replication following exposure of the immunized tonsils to HIV-1 infection (Breton et al., 2007).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Female BALB/c mice were used for immunizations. All were conducted on anesthetized mice. Immunizations with MVAs were accomplished by inoculating the desired amount of MVA into a single quadriceps muscle. Immunizations with DNA were accomplished by injecting the desired amount of DNA into the quadriceps, half in each leg (Liu et al., 2006).
  • Persistence: Temporal CD8 responses were conducted in BALB/c mice using MVA. Responses were steady for >10 weeks (>6 weeks post-MVA) (Liu et al., 2006).
  • Immune Response: CD8 T cells were boosted more effectively than CD4 T cells with the ratio of elicited CD8 to CD4 cells for the immunodominant CD8 epitope in Gag increasing with boosts. The most effective boost for CD8 T cells resulted in the greatest skewing of the CD8 to CD4 T cell ratio. This could represent better access of CD8 than CD4 T cells to APCs (Liu et al., 2006). The dose–response studies showed good increases for antigen expression with increasing MVA dose. A 1000-fold increase in the dose of MVA resulted in a 300-fold increase in the frequency of antigen-expressing cells. In contrast, dose–response studies for in vivo immunogenicity showed <10-fold increases in elicited T cells and Ab for 100–1000-fold increases in the dose of inoculated MVA. Shallow dose–response curves for immunogenicity were observed post priming as well as post boosting of an MVA or a DNA prime (Liu et al., 2006).
  • Side Effects: No adverse effects were encountered (Liu et al., 2006).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were immunized with two or three intranasal administrations of gp120/NE formulation at 3 weeks apart. The immunizations of 10 microliters were performed by slowly applying gp120/NE mixes to the nares.Control mice were immunized with gp120 in saline, with NE alone or saline. Intramuscular immunization was performed with two doses, 3 weeks apart, of 20 micrograms of gp120 injected in 50 microliters of either saline or 1% NE (Bielinska et al., 2008).
  • Immune Response: Immunized mice demonstrated robust serum anti-gp120 IgG, as well as bronchial, vaginal, and serum anti-gp120 IgA . The analysis of gp120-specific CTL proliferation, INF- induction, and prevalence of anti-gp120 IgG2 subclass antibodies indicated that nasal vaccination in NE also induced systemic, Th1-polarized cellular immune responses (Bielinska et al., 2008).

Mouse Response

  • Host Strain: C3H/HeN
  • Vaccination Protocol: Groups of five mice were immunized subcutaneously three times at 14-day intervals. The immunoliposomes were suspended in PBS and each mouse received 0.1 ml per injection. Each injection contained 380 &mu;g of PC, 193 &mu;g of CH, 10 pg of PE-B, 2.0 &mu;g of MAb, and 10 &mu;g of rgpl20 (Ozpolat et al., 1998).
  • Immune Response: Mice vaccinated with immunoliposomes were found to have a strong delayed-type hypersensitivity (DTH) response to the weakly immunogenic gp120 that was dependent on the presence of the MAbs. However, this vaccination protocol did not induce humoral immunity (Ozpolat et al., 1998).

Mouse Response

  • Host Strain: BABL/c
  • Vaccination Protocol: Mice were immunized with 10 μg of V3-VLPs without adjuvant in the muscle of the left leg. At the same time, the mice were immunized in the right leg with the other immunogens (Harris et al., 1996).
  • Immune Response: Mice immunized with V3 VLPs adjuvanted with gamma inulin showed good CTL responses (Harris et al., 1996).

Mouse Response

  • Vaccination Protocol: Mice were immunized two times subcutaneously at the base of the tail with PBS or 106 pfu of YF17D, YF-E/p24/NS1, or YF-5′/p24 in 100 μl on days 0 and 14 (Franco et al., 2010).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Three weeks after the second immunization, half of the mice in each group were challenged intranasally with 5 × 105 pfu of Gag-expressing recombinant vaccinia virus (Vac-gag). The remaining animals in the groups were challenged intranasally with the same dose of wild-type vaccinia virus (Vac-wt) (Franco et al., 2010).
  • Efficacy: The protective efficacy of the YF17D recombinants, particularly YF-E/p24/NS1, in mice challenged with a vaccinia expressing HIV-1 Gag was demonstrated (Franco et al., 2010).

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: A cocktail vaccine of V3014-packaged VRPs expressing the SIVsm H-4i nonmyristylated matrix-capsid region, full-length gp160, and a secreted form of gp160 (gp140) was used to immunize rhesus macaques. Animals were given each VRP subcutaneously in the arm and later were challenged by the intrarectal (IR) route. Control animals received an equivalent dose of HA-VRPs (Davis et al., 2002).
  • Immune Response: Both humoral and cellular immune responses were induced. On the day of challenge, all vaccinated animals had neutralizing antibody to the homologous SIVsm H-4, most had CTL specific for Gag, Env, or both. The animals were followed for a period of 40 weeks postchallenge, and although vaccination did not prevent infection by the high dose IR challenge, several protective effects of vaccination were seen. Peak virus titers in plasma were reduced, and the range of peak titers was much smaller for the controls, suggesting that a clear protective effect against the acute phase of infection was induced in some of the vaccinated animals (Davis et al., 2002).
  • Side Effects: No side effects were encountered (Davis et al., 2002).
  • Challenge Protocol: Animals were given a dose of VRP subcutaneously in the arm and 1 month later were challenged by the intrarectal (IR) route. Control animals received an equivalent dose of HA-VRPs. The challenge virus was the highly virulent swarm SIVsm E660 (Davis et al., 2002).
  • Efficacy: Animals were followed for a period of 40 weeks postchallenge, and although vaccination did not prevent infection by the high dose IR challenge, several protective effects of vaccination were seen. Four of six vaccinated animals, as compared to one of six controls, showed virus loads below 1,700 copies per ml at the “set point” (23 weeks postchallenge). By 41 weeks postchallenge, when the experiment was terminated, there was a significant decrease in the mean plasma virus load in the vaccinated animals compared to that in the controls. Most vaccinated animals showed virus loads below the “set point” (23 weeks postchallenge). By 41 weeks postchallenge, when the experiment was terminated, there was a significant decrease in the mean plasma virus load in the vaccinated animals compared to that in the controls. Finally, the CD4C cells of the vaccinated animals were preserved and even increased postchallenge compared to those of the controls. In fact, in the vaccinated animals, there is a clear correlation between increased CD4C cells and lowered viral load (Davis et al., 2002).

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).

Guinea pig Response

  • Host Strain: Hartley
  • Vaccination Protocol: Hartley guinea pigs were immunized intranasally with two administrations (50 microliters per nare) of gp120/NE mix at 3 weeks apart (Bielinska et al., 2008).
  • Immune Response: Immunization produced significant levels of serum anti-gp120 IgG antibodies in all animals, as was seen with the mice. The analysis of gp120-specific CTL proliferation, INF gamma induction, and prevalence of anti-gp120 IgG2 subclass antibodies indicated that nasal vaccination in NE also induced systemic, Th1-polarized cellular immune responses (Bielinska et al., 2008).
References References References References References References References References References References References References References References References
Gu et al., 2010: Gu R, Shampang A, Nashar T, Patil M, Fuller DH, Ramsingh AI. Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses. PloS one. 2010; 5(9); . [PubMed: 20824074].
Malm et al., 2005: Malm M, Rollman E, Ustav M, Hinkula J, Krohn K, Wahren B, Blazevic V. Cross-clade protection induced by human immunodeficiency virus-1 DNA immunogens expressing consensus sequences of multiple genes and epitopes from subtypes A, B, C, and FGH. Viral immunology. 2005; 18(4); 678-88. [PubMed: 16359234].
Caley et al., 1999: Caley IJ, Betts MR, Davis NL, Swanstrom R, Frelinger JA, Johnston RE. Venezuelan equine encephalitis virus vectors expressing HIV-1 proteins: vector design strategies for improved vaccine efficacy. Vaccine. 1999 Aug 6; 17(23-24); 3124-35. [PubMed: 10462249].
Davis et al., 2002: Davis NL, West A, Reap E, MacDonald G, Collier M, Dryga S, Maughan M, Connell M, Walker C, McGrath K, Cecil C, Ping LH, Frelinger J, Olmsted R, Keith P, Swanstrom R, Williamson C, Johnson P, Montefiori D, Johnston RE. Alphavirus replicon particles as candidate HIV vaccines. IUBMB life. 2002 Apr-May; 53(4-5); 209-11. [PubMed: 12120997].
Bomford et al., 1992: Bomford R, Stapleton M, Winsor S, McKnight A, Andronova T. The control of the antibody isotype response to recombinant human immunodeficiency virus gp120 antigen by adjuvants. AIDS research and human retroviruses. 1992; 8(10); 1765-1771. [PubMed: 1457190].
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