Simian Immunodeficiency Virus is a retrovirus that can infect at least 33 species of African primates. It has been present in primates for at least 32,000 years. Infections in the natural hosts appear to be generally non-pathogenic, except in the case of the Asian rhesus macaque, which will develop SAIDS (Wiki: Simian immunodeficiency virus).
>gi|9627209|ref|NP_054373.1| nef protein [Simian immunodeficiency virus]
MGSSNSKRQQQGLLKLWRGLRGKPGADWVLLSDPLIGQSSTVQEECGKALKKSWGKGKMTPDGRRLQEGD
TFDEWDDDEEEVGFPVQPRVPLRQMTYKLAVDFSHFLKSKGGLDGIYYSERREKILNLYALNEWGIIDDW
QAYSPGPGIRYPRVFGFCFKLVPVDLHEEARNCERHCLMHPAQMGEDPDGIDHGEVLVWKFDPKLAVEYR
PDMFKDMHEHAKR
Molecule Role :
Virmugen
Molecule Role Annotation :
A SIV nef mutant is attenuated in rhesus monkeys and induces protection from challenge with wild type SIV (Daniel et al., 1992).
Vaccination Protocol:
The macaques were divided into 5 groups. Group 1 (control group) received rBCG-PSO246 followed by two inoculations of rDIsLacZ. Group 2 (rBCG group) received rBCG-SIVgag followed by two inoculations of rDIsLacZ. Group 3 (rBCG/rDIs group) received rBCG-SIVgag followed by two inoculations of rDIsSIVgag. Group 4 (rDIS group) received two inoculations of rDIsSIVgag followed by rBCG-pSO246. Group 5 (rDIs/rBCG group) received two inoculations of rDIsSIVgag followed by rBCG-SIVgag (Ami et al., 2005).
Vaccine Immune Response Type:
VO_0003057
Challenge Protocol:
All groups were mucosally challenged with two thousand 50% tissue culture infectious doses of SHIV KS661c at 64 weeks after immunization, these were intrarectally administered (Ami et al., 2005).
Efficacy:
Only the macaques in group 3 (rBCG/rDIs) showed evidence of protective immune responses, the macaques in this group remained clinically healthy for a one year observation period. During this same observation period, by day 170, 6 macaques in the other 4 groups had died with symptoms consistent with simian AIDS. The rBCG/rDIs group vaccinated with the priming-boosting regimen had a superior survival rate than the other groups receiving vaccine protocols and the control group (Ami et al., 2005).
Description:
To construct pSabRV1, first the EcoRI and XhoI sites upstream of the T7 promoter of pS1 were eliminated to create plasmid pS1XT. Then the 747-bp BstEII fragment of pMoV2.11—containing the duplicated 2Apro cleavage site, the 5-glycine spacer, and the EcoRI, NotI, and XhoI cloning sites—was swapped into pS1XT to create pSabRV1 (Crotty et al., 2001).
f. Gene Engineering of
env receptor binding subunit
Type:
Recombinant vector construction
Description:
To construct pSabRV1, first the EcoRI and XhoI sites upstream of the T7 promoter of pS1 were eliminated to create plasmid pS1XT. Then the 747-bp BstEII fragment of pMoV2.11—containing the duplicated 2Apro cleavage site, the 5-glycine spacer, and the EcoRI, NotI, and XhoI cloning sites—was swapped into pS1XT to create pSabRV1 (Crotty et al., 2001).
Description:
To construct pSabRV1, first the EcoRI and XhoI sites upstream of the T7 promoter of pS1 were eliminated to create plasmid pS1XT. Then the 747-bp BstEII fragment of pMoV2.11—containing the duplicated 2Apro cleavage site, the 5-glycine spacer, and the EcoRI, NotI, and XhoI cloning sites—was swapped into pS1XT to create pSabRV1 (Crotty et al., 2001).
New poliovirus vectors based on Sabin 1 and 2 vaccine strain viruses were constructed, and these vectors were used to generate a series of new viruses containing SIV gag, pol, env, nef, and tat in overlapping fragments (Crotty et al., 2001).
i. Immunization Route
Intramuscular injection (i.m.)
j.
Macaque Response
Vaccination Protocol:
Seven animals were inoculated intranasally with 1 ml (5 × 10^7 PFU) of SabRV1-SIV on days 1, 3, 14, and 16, for a total of four immunizations. Nineteen weeks after the first series of inoculations, these same seven animals were given boosters of two intranasal inoculations of 1 ml (10^6 PFU/ml) of SabRV2-SIV, one at week 19 and a second at week 21 (Crotty et al., 2001).
Vaccine Immune Response Type:
VO_0003057
Challenge Protocol:
The animals were challenged with 10^5 TCID50 of SIVmac251 intravaginally, using the SIVmac251 (5/98) stock (Crotty et al., 2001).
Efficacy:
Four of the seven vaccinated animals exhibited substantial protection against the vaginal SIV challenge (Crotty et al., 2001).
Efficacy:
The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone (Boyer et al., 2007).
6. SIV DNA vaccine pVacc4 encoding env from mac239
Efficacy:
After rectal challenge of vaccinated and naive animals with SHIV89.6P, all animals became infected. However a subset were protected from CD4+ T cell loss and AIDS development. Thus, nasal vaccination with SHIV-DNA plus IL-2/Ig DNA and rMVA can provide significant protection from disease progression (Bertley et al., 2004).
a mismatched SIV envelope (Env) gene derived from simian immunodeficiency virus SIVmac239 (Flatz et al., 2012)
f. Vector:
Recombinant adenovirus type 5 (rAd5) priming, replication-defective lymphocytic choriomeningitis virus boosting (Flatz et al., 2012)
g. Immunization Route
Intramuscular injection (i.m.)
h.
Macaque Response
Vaccine Immune Response Type:
VO_0003057
Immune Response:
Recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. In addition, there was a presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells (Flatz et al., 2012).
Efficacy:
To evaluate the infectibility of immunized and control animals, 10 vaccinated Macaca mulatta animals and 10 controls were challenged intrarectally with SIVsmE660 six weeks after the rLCMV boost. In the vaccinated group, three of the 10 monkeys became infected after 99 challenges (3% infection rate per challenge), while in the control null group, eight of the 10 monkeys were infected after 47 challenges (17% infection rate per challenge), indicating a protective efficacy of 82% per challenge (Flatz et al., 2012).
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5. Boyer et al., 2005: Boyer JD, Robinson TM, Kutzler MA, Parkinson R, Calarota SA, Sidhu MK, Muthumani K, Lewis M, Pavlakis G, Felber B, Weiner D. SIV DNA vaccine co-administered with IL-12 expression plasmid enhances CD8 SIV cellular immune responses in cynomolgus macaques. Journal of medical primatology. 2005; 34(5-6); 262-270. [PubMed: 16128921].
6. Boyer et al., 2007: Boyer JD, Robinson TM, Kutzler MA, Vansant G, Hokey DA, Kumar S, Parkinson R, Wu L, Sidhu MK, Pavlakis GN, Felber BK, Brown C, Silvera P, Lewis MG, Monforte J, Waldmann TA, Eldridge J, Weiner DB. Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid. Proceedings of the National Academy of Sciences of the United States of America. 2007; 104(47); 18648-18653. [PubMed: 18000037].
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8. Crotty et al., 2001: Crotty S, Miller CJ, Lohman BL, Neagu MR, Compton L, Lu D, Lü FX, Fritts L, Lifson JD, Andino R. Protection against simian immunodeficiency virus vaginal challenge by using Sabin poliovirus vectors. Journal of virology. 2001; 75(16); 7435-7452. [PubMed: 11462016].
9. Daniel et al., 1992: Daniel MD, Kirchhoff F, Czajak SC, Sehgal PK, Desrosiers RC. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science (New York, N.Y.). 1992; 258(5090); 1938-1941. [PubMed: 1470917].
10. Flatz et al., 2012: Flatz L, Cheng C, Wang L, Foulds KE, Ko SY, Kong WP, Roychoudhuri R, Shi W, Bao S, Todd JP, Asmal M, Shen L, Donaldson M, Schmidt SD, Gall JG, Pinschewer DD, Letvin NL, Rao S, Mascola JR, Roederer M, Nabel GJ. Gene-based vaccination with a mismatched envelope protects against simian immunodeficiency virus infection in nonhuman primates. Journal of virology. 2012; 86(15); 7760-7770. [PubMed: 22593152].
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