VIOLIN Logo
VO Banner
Search: for Help
About
Introduction
Statistics
VIOLIN News
Your VIOLIN
Register or Login
Submission
Tutorial
Vaccine & Components
Vaxquery
Vaxgen
VBLAST
Protegen
VirmugenDB
DNAVaxDB
CanVaxKB
Vaxjo
Vaxvec
Vevax
Huvax
Vaccine Mechanisms
Vaximmutordb
Vaxism
Vaxar
Vaccine Literature
VO-SciMiner
Litesearch
Vaxmesh
Vaxlert
Vaccine Design
Vaxign
Community Efforts
Vaccine Ontology
ICoVax 2012
ICoVax 2013
Advisory Committee
Vaccine Society
Vaxperts
VaxPub
VaxCom
VaxLaw
VaxMedia
VaxMeet
VaxFund
VaxCareer
Data Exchange
V-Utilities
VIOLINML
Help & Documents
Publications
Documents
FAQs
Links
Acknowledgements
Disclaimer
Contact Us
UMMS Logo

Vaccine Comparison

Adenoviral vector Ad5 expressing SIV gag protein ALVAC-HIV-2 ALVAC-HIV-2- env/gag/pol DNA and poxvirus priming-boosting SHIV vaccine Gag-VRPs HIV DNA and adenoviral vector Ad5 expressing SIV gag protein HIV DNA vaccine VlJns-tPA-gp120 HIV priming with DNA vaccine expressing HIV gp160 protein and boosted with Ad5/35 vector expressing the same protein HIV recombinant vector vaccine MVA-gag encoding gag HIV-1 gp120 with mCT E112K rMVTT-SIV-gpe
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_0000788
  • Type: Recombinant vector vaccine
  • Status: Research
  • Antigen: SIVmac239 gag protein (Shiver et al., 2002)
  • Gag protein from SIV-mnd 2 gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • Vector: Adenoviral vector (Ad5)
  • Preparation: The adenoviral vector was based on a serotype 5 adenovirus that is incompetent to replicate with deletion of the E1 and E3 viral genes, and was propagated subsequently in E1-expressing 293 cells. Recombinant adenovirus expressing the codon-optimized SIV gag gene was then prepared. The recombinant adenovirus (Ad5-SIVgag) was grown in large quantities by multiple rounds of amplification in 293 cells. The virus was purified by caesium chloride gradient centrifugation (Shiver et al., 2002).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004727
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • env gene engineering:
    • Type: Recombinant vector construction
    • Description: Live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
    • Detailed Gene Information: Click Here.
  • gag gene engineering:
    • Type: Recombinant vector construction
    • Description: Live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
    • Detailed Gene Information: Click Here.
  • Preparation: A live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004737
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • env gene engineering:
    • Type: Recombinant vector construction
    • Description: Live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine alone versus boosting with live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
    • Detailed Gene Information: Click Here.
  • gag gene engineering:
    • Type: Recombinant vector construction
    • Description: Live attenuated human immunodeficiency virus type 2 (HIV-2) vaccine alone versus boosting with live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
    • Detailed Gene Information: Click Here.
  • Preparation: A live non-pathogenic HIV-2 following priming with ALVAC HIV-2 (recombinant canarypox virus expressing HIV-2 env, gag and pol) (Walther-Jallow et al., 2001).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0000825
  • Type: DNA vaccine
  • Antigen: SHIV89.6P env and SIVmac239 gag (Santra et al., 2004)
  • env gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Gag protein from SIV-mnd 2 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: pV1R plasmid and recombinant fowlpox virus
  • Preparation: The recombinant vaccinia viruses (rVac) expressing SHIV89.6P env and SIVmac239 gag were constructed by inserting these genes in the HindIII M region of TBC-Wy, Therion strain of vaccinia. rFPV viruses expressing these same genes were constructed by inserting the genes in the BamJHI region of POXVAC-TC (Schering-Plough) strain of FPV (Santra et al., 2004).
  • Description: An HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, but the characteristics of effective vaccine-induced CTL response remain unclear. The SHIV/rhesus monkey model has been used to in the course of assessing the relative immunogenicity of vaccine regimens that include a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. This study indicates that the steady-state memory, rather than the peak effector vaccine-elicited CTL responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine (Santra et al., 2004).
  • 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_0000786
  • Type: DNA vaccine
  • Status: Research
  • Antigen: SIVmac239 gag protein (Shiver et al., 2002)
  • Gag protein from SIV-mnd 2 gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • Gag protein from SIV-mnd 2 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Adjuvant: CRL1005
  • Vector: V1R plasmid and adenoviral vector (Ad5)
  • Preparation: The V1R DNA vector expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells (Shiver et al., 2002). The plasmid DNA vector was formulated in a solution containing a nonionic blocked copolymer adjuvant (CRL1005) (Shiver et al., 2002).
    The adenoviral vector was based on a serotype 5 adenovirus that is incompetent to replicate with deletion of the E1 and E3 viral genes, and was propagated subsequently in E1-expressing 293 cells. Recombinant adenovirus expressing the codon-optimized SIV gag gene was then prepared. The recombinant adenovirus (Ad5-SIVgag) was grown in large quantities by multiple rounds of amplification in 293 cells. The virus was purified by caesium chloride gradient centrifugation (Shiver et al., 2002).
  • Immunization Route: Intramuscular injection (i.m.)
  • Virulence: No virulence has been reported associated with this vaccine (Shiver et al., 2002).
  • Description: Immunization and viral challenge studies were conducted in rhesus macaques (Macaca mulatta). Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. The plasmid DNA vector was formulated in either PBS solution, a solution containing adjuvant, or a solution containing MPL/alum. All immunized animals were genotyped for the MHC class I Mamu-A*01 allele, allowing analysis of the responses of T cells (CD8+) to the test vaccines (Shiver et al., 2002).
  • Vaccine Ontology ID: VO_0004351
  • Type: DNA vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Rhesus monkey
  • gp120 gene engineering:
    • Type: DNA vaccine construction
    • Description: This vaccine encoded gp120 from HIV IIIB (Lekutis et al., 1997).
    • Detailed Gene Information: Click Here.
  • Vector: VlJns (Lekutis et al., 1997)
  • 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_0004347
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Macaque
  • Gag from HIV 1 gene engineering:
    • Type: Recombinant vector construction
    • Description: This recombinant vector vaccine expressed gag from HIV-1 (Casimiro et al., 2003).
    • Detailed Gene Information: Click Here.
  • Vector: pSC59 (Casimiro et al., 2003).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004268
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: HIV-1LAIEnv gp120 (Yoshino et al., 2004).
  • Adjuvant: non-toxic mutant E112K of Cholera Toxin mCT-E112K
  • Immunization Route: intranasal immunization
  • Vaccine Ontology ID: VO_0004760
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • env from SIV gene engineering:
    • Type: Recombinant vector construction
    • Description: A recombinant modified replicating vaccinia virus Tiantan strain (MVTTSIVgpe) and a recombinant, nonreplicating adenovirus type 5 strain (Ad5SIVgpe) expressing the SIVmac239 Gag, Pol, and Env structural proteins were generated (Sun et al., 2013).
    • Detailed Gene Information: Click Here.
  • Pol SIV gene engineering:
    • Type: Recombinant vector construction
    • Description: A recombinant modified replicating vaccinia virus Tiantan strain (MVTTSIVgpe) and a recombinant, nonreplicating adenovirus type 5 strain (Ad5SIVgpe) expressing the SIVmac239 Gag, Pol, and Env structural proteins were generated (Sun et al., 2013).
    • Detailed Gene Information: Click Here.
  • Pol SIV gene engineering:
    • Type: Recombinant vector construction
    • Description: A recombinant modified replicating vaccinia virus Tiantan strain (MVTTSIVgpe) and a recombinant, nonreplicating adenovirus type 5 strain (Ad5SIVgpe) expressing the SIVmac239 Gag, Pol, and Env structural proteins were generated (Sun et al., 2013).
    • Detailed Gene Information: Click Here.
  • Preparation: (Sun et al., 2013) a modified replicating vaccinia virus Tiantan strain (MVTT(SIVgpe))
  • 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

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

  • 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).

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: In this study, 21 rhesus monkeys were divided into 6 groups, including an unimmunized control cohort. Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. In the first study, the two viral vector vaccines were administered, followed by a booster dose; preparations of DNA plasmid vector vaccine were delivered thrice, followed by a booster (Shiver et al., 2002).
  • Immune Response: In general, all of the monkeys developed p11CM-specific cellular immune responses after the initial immunization series. The p11CM (residues 181–189) is an immunodominant SIV gag epitope that is presented by the Mamu-A*01 MHC protein and is capable of binding T-cell receptors in the model monkeys. Administration of the third dose of the Ad5 vector resulted in an additional increase of p11CM-specific CD8+ T cells at the time of virus challenge. After the booster inoculation, these animals exhibited peak levels of p11CM-specific CD8+ T cells (Shiver et al., 2002).
  • Challenge Protocol: At 12 weeks after the final immunization, all monkeys were challenged i.v. with the pathogenic HIV–SIV hybrid virus (SHIV) 89.6P16. The challenge of the control and immunized animals within the context of each of the two independent studies occurred concurrently (Shiver et al., 2002).
  • Efficacy: Each of the animals in both control groups exhibited acute CD4+ T-cell lymphopenia and peak viral loads of viral RNA copies at about 3 weeks after challenge. With the exception of one animal, all of the control monkeys experienced dramatic loss of CD4+ T cells. During the acute phase of the infection, most monkeys immunized with either the DNA or MVA vectors exhibit an acute CD4+ T-cell lymphopenia. By about 70 d after challenge, many of the immunized monkeys exhibit some evidence of a positive immunization benefit, as manifested by control of viremia and recovery of CD4+ T-cell counts. However, the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the infection with a pathogenic HIV–SIV hybrid virus (SHIV) (Shiver et al., 2002).

Monkey Response

  • Vaccination Protocol: Five monkeys were immunized either three times with ALVAC HIV-2 alone or twice with ALVAC HIV-2 and once with purified native HIV-2 gp125 (Walther-Jallow et al., 2001).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: The monkeys were then challenged with HIV-2 given intravenously and finally with pathogenic SIVsm given intrarectally (Walther-Jallow et al., 2001).
  • Efficacy: After challenge with SIVsm, three of five monkeys were completely protected against SIVsm infection. Vaccination with an ALVAC HIV-2 vaccine followed by exposure to live HIV-2 could induce cross-protection against mucosal infection with SIVsm and seemed to be more efficient than immunization with a live HIV-2 vaccine only (Walther-Jallow et al., 2001).

Monkey Response

  • Vaccination Protocol: Six monkeys were first inoculated intravenously with live HIV-2(SBL-6669) (Walther-Jallow et al., 2001).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: 7 to 10 months after vaccination, the monkeys were challenged intrarectally with 10 MID(50) of cell-free simian immunodeficiency virus (SIV) strain SIVsm (Walther-Jallow et al., 2001).
  • Efficacy: Vaccination with an ALVAC HIV-2 vaccine followed by exposure to live HIV-2 could induce cross-protection against mucosal infection with SIVsm and seemed to be more efficient than immunization with a live HIV-2 vaccine only (Walther-Jallow et al., 2001).

Monkey Response

  • Host Strain: rhesus monkey (Macaca mulatta)
  • Vaccination Protocol: Nonrecombinant wildtype vaccinia virus was designated VV-WT, wild-type fowlpox virus was designated FPV-WT, and wild-type MVA was designated MVA-WT. These wild-type viruses were used as control vector immunogens (Santra et al., 2004). One group of monkeys were vaccinated by separate i.m. injections of HIV-1. Half the dose was delivered to each quadriceps muscle. Seven of the 28 monkeys were vaccinated by both i.d. and i.m. injections of rFPV expressing HIV-1 89.6P Env and the same virus expressing SIV mac239 Gag. Seven monkeys received rMVA-HIV-189.6P Env and rMVA-SIVmac239 Gag, and another seven monkeys received rVac-HIV-1 89.6P Env and rVac-SIVmac239 Gag administered both i.d. and i.m. Another 28 monkeys received sham plasmid DNA and empty pox vectors (Santra et al., 2004).
  • Persistence: Persistence levels were measured 2 weeks after challenge with results mentioned in Challenge Protocol section (Santra et al., 2004).
  • Immune Response: Recombinant vaccinia virus, MVA, and fowlpox were comparable in their immunogenicity. Magnitude of peak vaccine-elicited CTL responses in pox virus-boosted monkeys is substantially greater than that seen in monkeys immunized with plasmid DNA alone, but magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone vaccinated monkeys by the time of viral challenge. Clinical protection seen in all groups of experimentally vaccinated monkeys is similar, indicating that steady-state memory, rather than peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine (Santra et al., 2004).
  • Challenge Protocol: Eighteen weeks after the final immunization, all animals were challenged with cell-free SHIV-89.6P i.v. (Santra et al., 2004).
  • Efficacy: Control monkeys developed tetramer-binding CD8 T lymphocyte responses that were maximal 2 weeks after viral challenge and no detectable p41A-specific CD8 T cells. In contrast, all four groups of vaccinated monkeys developed robust secondary p11C-specific CTL responses that were comparable in magnitude. Animals boosted with plasmid DNA had Gag p11C-specific CD8 T cell responses similar in magnitude to that seen in the recombinant pox virus-boosted animals. Magnitudes of the postchallenge IFN ELISPOT responses to both vaccine antigens were comparable in all four experimentally vaccinated groups of monkeys. Therefore, although the pre-challenge peak vaccine-elicited immune responses were greater in the groups of monkeys boosted with recombinant pox vectors, the pre-challenge plateau and post-challenge peak secondary responses were equivalent in magnitude in all four experimental groups of animals (Santra et al., 2004).
  • Host IFNG response
    • Description: There was a greater contraction of the vaccine-elicited IFN-γ-secreting T cell responses in the groups of monkeys boosted with recombinant pox vectors than in the group of animals boosted with plasmid DNA. Although the pre-challenge peak vaccine-elicited immune responses were greater in the groups of monkeys boosted with recombinant pox vectors, the pre-challenge plateau and post-challenge peak secondary responses were equivalent in magnitude in all four experimental groups of animals (Santra et al., 2004).
    • Detailed Gene Information: Click Here.

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: This study used 14 monkeys, 3 each in the immunized groups and 8 in the unimmunized control group. Each of the test vectors expressed the identical SIVmac239 gag gene that had been codon optimized for expression in mammalian cells. The DNA vector priming inoculations were administered, followed by viral vector boost inoculations (Shiver et al., 2002).
  • Immune Response: In general, all of the monkeys developed p11CM-specific cellular immune responses after the initial immunization series. The p11CM (residues 181–189) is an immunodominant SIV gag epitope that is presented by the Mamu-A*01 MHC protein and is capable of binding T-cell receptors in the model monkeys. Administration of the third dose of the Ad5 vector resulted in an additional increase of p11CM-specific CD8+ T cells at the time of virus challenge. After the booster inoculation, these animals exhibited peak levels of p11CM-specific CD8+ T cells (Shiver et al., 2002).
  • Side Effects: None of the vaccinated monkeys have yet exhibited any signs of immunodeficiency or suffered any consistent weight loss (Shiver et al., 2002).
  • Challenge Protocol: At 6 weeks after the final immunization, all monkeys were challenged i.v. with the pathogenic HIV–SIV hybrid virus (SHIV) 89.6P16. The challenge of the control and immunized animals within the context of each of the two independent studies occurred concurrently (Shiver et al., 2002).
  • Efficacy: Each of the animals in both control groups exhibited acute CD4+ T-cell lymphopenia and peak viral loads of viral RNA copies at about 3 weeks after challenge. All of the control monkeys experienced dramatic loss of CD4+ T cells. During the acute phase of the infection, most monkeys immunized with either the DNA or MVA vectors or with the DNA/CRL1005–MVA vector prime–boost combination exhibit an acute CD4+ T-cell lymphopenia. By about 70 d after challenge, many of the immunized monkeys exhibit some evidence of a positive immunization benefit, as manifested by control of viremia and recovery of CD4+ T-cell counts. However, the animals immunized with Ad5 vector exhibited the most pronounced attenuation of the infection with a pathogenic HIV–SIV hybrid virus (SHIV) (Shiver et al., 2002).
  • Host IFNG response
    • Description: Levels of interferon-gamma in monkeys stimulated intramuscularly with either the p11CM peptide or a pool of peptides derived from SIV gag were significantly upregulated and correlated well with the tetramer-staining results after the final boost. Intracellular IFN-[gamma]-staining assays confirmed that these responses were primarily mediated by CD8+ T cells (Shiver et al., 2002).
    • Detailed Gene Information: Click Here.

Monkey Response

  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: The secretion of IFN-y stimulated CD4+ Th cell lines and rgp120-stimulated PBL from the vaccinated monkeys suggest that an HIV-1 env plasmid DNA vaccine elicits a Thl-like immune response in primates as well as in rodents (Lekutis et al., 1997)
  • Efficacy: The secondary immune response that arose after repeated plasmid DNA administration was Thl-like, suggesting that the nature of the DNA vaccine-elicited Th cell response was maturation dependent. Evidence from vaccinated nonhuman primates suggests that a vigorous Th cell response, including viral Ag-specific IFN-y production, may be a correlate of protection from HIV- 1 and Simian Human Immunodeficiency Virus infection (Lekutis et al., 1997)

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).

Monkey Response

  • Vaccine Immune Response Type: VO_0000286
  • Immune Response: Immunization of macaques with MVA-gag resulted in relatively weak antigen-specific T-cell responses; the levels did not exceed 150 spot-forming cells (SFC)/106 PBMCs after three doses and were significantly less than those observed in the Ad5-gag vaccinees. Only one of six MVA-gag vaccinees elicited any detectable Gag-specific antibody response (140 mMU/ml at 4 weeks post-dose 3 for monkey V215) (Casimiro et al., 2003).
  • Efficacy: The study reports that SIV Gag delivered by DNA, MVA, or adenovirus type 5 vectors is able to inhibit viral replication and disease progression in rhesus macaques following challenge with the SHIV89.6P virus. However, only 50% of the animals that received MVA alone or in combination with DNA were able to effectively control viremia (Casimiro et al., 2003).

Monkey Response

  • Host Strain: rhesus macaques
  • Vaccination Protocol: Rhesus macaques were divided into four groups and nasally immunized with vaccine containing: 1) 100 µg of gp120 alone, 2) 100 µg of gp120 plus 10 µg of nCT, 3) 100 µg of gp120 plus 25 µg of mCT E112K, or 4) 100 µg of gp120 plus 100 µg of mCT E112K. Macaques were anesthetized with ketamine and placed in dorsal recumbancy with head tilted back so that the nares were pointed upward. Vaccine solution (0.5 ml) was instilled dropwise into each nostril without inserting the syringe into the nasal cavity. Macaques were kept in that position for 10 min and then placed in lateral recumbancy until they recovered from anesthesia, as described previously (16). Nasal immunization was conducted on days 0, 7, 14, 28, 42, and 56 (Yoshino et al., 2004).
  • Immune Response: Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4(+)) T cells than did controls. Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups (Yoshino et al., 2004).
  • Host IgA Fc fragment response
    • Description: Macaques given nasal gp120 with either mCT E112K or nCT showed significantly elevated IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues compared to controls, who were vaccinated without the adjuvant (Yoshino et al., 2004).
    • Detailed Gene Information: Click Here.
  • Host IgG Fc fragment response
    • Description: Macaques given nasal gp120 with either mCT E112K or nCT showed significantly elevated gp120-specific IgG responses with virus-neutralizing activity in both their plasma and mucosal external secretions compared to controls, who were vaccinated without the adjuvant (Yoshino et al., 2004).
    • Detailed Gene Information: Click Here.
  • Host IL4 response
    • Description: Vaccinated animals that received the adjuvant had a greater increase in IL-4-producing Th2-type CD4-positive (CD4(+)) T cells in mesenteric lymph nodes (MLNs) than did controls vaccinated without the adjuvant, which did not produce IL-4 (Yoshino et al., 2004),
    • Detailed Gene Information: Click Here.

Monkey Response

  • Vaccination Protocol: Eight monkeys were divided into two groups: (i) four monkeys received the MVTTioin+Adim testing regimen as in study I, and (ii) four monkeys received an empty MVTT control vector (109 PFU) through intraoral (0.5 ml) and intranasal (0.5 ml) routes and an empty Ad5 control vector (1011 vp in 1 ml of PBS) through intramuscular injection (Sun et al., 2013).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: At either week 30 after the initial vaccination or week 24 after the final vaccination, each animal was challenged intrarectally with 5 × 105 50% tissue culture infective doses (TCID50) of Chinese rhesus monkey-adapted and neutralization-resistant SIVmac239. In all cases, the challenge virus stock was administered in 1 ml of PBS (Sun et al., 2013).
  • Efficacy: The reductions in peak and set-point viral loads were significant in most animals, with one other animal being protected fully from high-dose intrarectal inoculation of SIV(mac239). Furthermore, the animals vaccinated with this regimen were healthy, while ~75% of control animals developed simian AIDS. The protective effects correlated with the vaccine-elicited SIV-specific CD8(+) T cell responses against Gag and Pol (Sun et al., 2013).
References References References References References References References References References References References
Shiver et al., 2002: Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17; 415(6869); 331-5. [PubMed: 11797011].
Walther-Jallow et al., 2001: Walther-Jallow L, Nilsson C, Söderlund J, ten Haaft P, Mäkitalo B, Biberfeld P, Böttiger P, Heeney J, Biberfeld G, Thorstensson R. Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys. The Journal of general virology. 2001; 82(Pt 7); 1601-1612. [PubMed: 11413371].
Walther-Jallow et al., 2001: Walther-Jallow L, Nilsson C, Söderlund J, ten Haaft P, Mäkitalo B, Biberfeld P, Böttiger P, Heeney J, Biberfeld G, Thorstensson R. Cross-protection against mucosal simian immunodeficiency virus (SIVsm) challenge in human immunodeficiency virus type 2-vaccinated cynomolgus monkeys. The Journal of general virology. 2001; 82(Pt 7); 1601-1612. [PubMed: 11413371].
Santra et al., 2004: Santra S, Barouch DH, Korioth-Schmitz B, Lord CI, Krivulka GR, Yu F, Beddall MH, Gorgone DA, Lifton MA, Miura A, Philippon V, Manson K, Markham PD, Parrish J, Kuroda MJ, Schmitz JE, Gelman RS, Shiver JW, Montefiori DC, Panicali D, Letvin NL. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses. Proceedings of the National Academy of Sciences of the United States of America. 2004 Jul 27; 101(30); 11088-93. [PubMed: 15258286].
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].
Shiver et al., 2002: Shiver JW, Fu TM, Chen L, Casimiro DR, Davies ME, Evans RK, Zhang ZQ, Simon AJ, Trigona WL, Dubey SA, Huang L, Harris VA, Long RS, Liang X, Handt L, Schleif WA, Zhu L, Freed DC, Persaud NV, Guan L, Punt KS, Tang A, Chen M, Wilson KA, Collins KB, Heidecker GJ, Fernandez VR, Perry HC, Joyce JG, Grimm KM, Cook JC, Keller PM, Kresock DS, Mach H, Troutman RD, Isopi LA, Williams DM, Xu Z, Bohannon KE, Volkin DB, Montefiori DC, Miura A, Krivulka GR, Lifton MA, Kuroda MJ, Schmitz JE, Letvin NL, Caulfield MJ, Bett AJ, Youil R, Kaslow DC, Emini EA. Replication-incompetent adenoviral vaccine vector elicits effective anti-immunodeficiency-virus immunity. Nature. 2002 Jan 17; 415(6869); 331-5. [PubMed: 11797011].
Lekutis et al., 1997: Lekutis C, Shiver JW, Liu MA, Letvin NL. HIV-1 env DNA vaccine administered to rhesus monkeys elicits MHC class II-restricted CD4+ T helper cells that secrete IFN-gamma and TNF-alpha. Journal of immunology (Baltimore, Md. : 1950). 1997; 158(9); 4471-4477. [PubMed: 9127013].
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].
Casimiro et al., 2003: Casimiro DR, Chen L, Fu TM, Evans RK, Caulfield MJ, Davies ME, Tang A, Chen M, Huang L, Harris V, Freed DC, Wilson KA, Dubey S, Zhu DM, Nawrocki D, Mach H, Troutman R, Isopi L, Williams D, Hurni W, Xu Z, Smith JG, Wang S, Liu X, Guan L, Long R, Trigona W, Heidecker GJ, Perry HC, Persaud N, Toner TJ, Su Q, Liang X, Youil R, Chastain M, Bett AJ, Volkin DB, Emini EA, Shiver JW. Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene. Journal of virology. 2003; 77(11); 6305-6313. [PubMed: 12743287].
Yoshino et al., 2004: Yoshino N, Lü FX, Fujihashi K, Hagiwara Y, Kataoka K, Lu D, Hirst L, Honda M, van Ginkel FW, Takeda Y, Miller CJ, Kiyono H, McGhee JR. A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates. Journal of immunology (Baltimore, Md. : 1950). 2004; 173(11); 6850-6857. [PubMed: 15557179].
Sun et al., 2013: Sun C, Chen Z, Tang X, Zhang Y, Feng L, Du Y, Xiao L, Liu L, Zhu W, Chen L, Zhang L. Mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys. Journal of virology. 2013; 87(10); 5669-5677. [PubMed: 23487457].