Mucosally-administered human–simian immunodeficiency virus DNA and fowlpoxvirus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIVSF162P3

Kent, Stephen J.; Dale, C. Jane; Ranasinghe, Charani; Stratov, Ivan; Rose, Robert De; Chea, Socheata; Montefiori, David C.; Thomson, Scott; Ramshaw, Ian A.; Coupar, Barbara E.H.; Boyle, David B.; Law, Matthew; Wilson, Kim; Ramsay, Alistair J.

doi:10.1016/j.vaccine.2005.05.032

Cited by 58 publications

(52 citation statements)

References 40 publications

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“…[1][2][3][4] The bacterial microbiota in the lower genital tract of pigtailed macaques could have an impact on vaginal infection with SIV or SHIV since in humans, epidemiological studies indicate that women with a genital microbiota that has the characteristics of bacterial vaginosis have a significantly increased susceptibility to sexual transmission of HIV. [5][6][7] Bacterial vaginosis (BV) is a condition in women in which the predominant genital bacterial types are a polymicrobial and variable mixture of bacteria including Gardnerella vaginalis, Prevotella, bacteria in the Order Clostridiales, and other anaerobes.…”

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confidence: 99%

Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

Spear

Kersh

Guenthner

et al. 2012

AIDS Research and Human Retroviruses

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Vaginal bacterial communities play an important role in human health and have been shown to influence HIV infection. Pigtailed macaques (Macaca nemestrina) are used as an animal model of HIV vaginal infection of women. Since the bacterial microbiota could influence retrovirus infection of pigtailed macaques, the genital microbiota in 10 cycling macaques was determined by pyrosequencing. The microbiota of all macaques was polymicrobial with a median of 13 distinct genera. Strikingly, the genera Sneathia and Fusobacterium, both in the phylum Fusobacteria, accounted for 18.9% and 13.3% of sequences while the next most frequent were Prevotella (5.6%), Porphyromonas (4.1%), Atopobium (3.6%), and Parvimonas (2.6%). Sequences corresponding to Lactobacillus comprised only 2.2% of sequences on average and were essentially all L. amylovorus. Longitudinal sampling of the 10 macaques over an 8-week period, which spanned at least one full ovulatory cycle, showed a generally stable presence of the major types of bacteria with some exceptions. These studies show that the microbiota of the pigtailed macaques is substantially dissimilar to that found in most healthy humans, where the genital microbiota is usually dominated by Lactobacillus sp. The polymicrobial makeup of the macaque bacterial populations, the paucity of lactobacilli, and the specific types of bacteria present suggest that the pigtailed macaque microbiota could influence vaginal retrovirus infection.

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Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

Spear

Kersh

Guenthner

et al. 2012

AIDS Research and Human Retroviruses

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“…The circulating recombinant subtype AE is common in many Southeast Asian countries, including Thailand, although no preclinical efficacy studies or clinical trials with subtype AE vaccines have been reported. We previously demonstrated the safety and immunogenicity of subtype AE HIV-1 DNA and FPV vaccines in macaques (12), modeled on our previous macaque and human work with subtype B HIV-1 and SHIV vaccines (8,9,(18)(19)(20). In this study we analyzed a set of subtype AE SHIV vaccines expressing SIV Gag and Pol and HIV-1 subtype AE Env, Tat, and Rev for immunogenicity and efficacy in pigtail macaques.…”

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Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

Rose

Batten

Smith

et al. 2007

J Virol

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Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log 10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.

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“…CD4 T-cell depletion (A) and SHIV viremia (B) in both animals were analyzed and compared to the means Ϯ standard errors for six animals previously infected with the parent SHIV mn229 (4). (C and D) Macaques 5904 and 6175 were inoculated with escape mutant AF9 virus with a 6-bp deletion (AF9 EM), and viral loads were compared to the mean viral load of eight naïve animals previously inoculated with the R5-tropic parent virus SHIV SF162P3 as above (9). viral quasispecies and promote more rapid reversion.…”

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confidence: 99%

“…Based on a detailed study of escape and reversion kinetics at a single Mane-A*10-restricted SIV Gag CD8 T-cell epitope (Gag 164-172 KP9), we previously hypothesized that the effectiveness of particular T cells could be measured by analyzing the rate of clearance of wild-type virus during T-cell escape (6,10). To investigate this rate at other epitopes, we studied escape kinetics at two additional previously defined dominant SIV mac239 Gag CD8 ϩ T-cell epitopes, KW9 (Gag 28-36 ) and AF9 (Gag 371-379 ), in DNA-and fowlpoxvirus-immunized pigtail macaques (4)(5)(6)9). The MHC restrictions of these two epitopes are Mane-B*10 and Mane-A*17, respectively (16,17).…”

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confidence: 99%

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In Vivo Fitness Costs of Different Gag CD8 T-Cell Escape Mutant Simian-Human Immunodeficiency Viruses for Macaques

Loh

Batten

Petravic

et al. 2007

J Virol

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The kinetics of immune escape and reversion depend upon the efficiency of CD8 cytotoxic T lymphocytes (CTL) and the fitness cost of escape mutations. Escape kinetics of three simian immunodeficiency virus Gag CTL epitopes in pigtail macaques were variable; those of KP9 and AF9 were faster than those of KW9. Kinetics of reversion of escape mutant virus to wild type upon passage to naïve major histocompatibility complexmismatched macaques also varied. Rapid reversion occurred at KP9, gradual biphasic reversion occurred at AF9, and escape mutant KW9 virus failed to revert. The fitness impact of these mutations is KP9 > AF9 > KW9. These data provide insights into the differential utility of CTL in controlling viremia.

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Mucosally-administered human–simian immunodeficiency virus DNA and fowlpoxvirus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIVSF162P3

Cited by 58 publications

References 40 publications

Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

Longitudinal Assessment of Pigtailed Macaque Lower Genital Tract Microbiota by Pyrosequencing Reveals Dissimilarity to the Genital Microbiota of Healthy Humans

Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques

In Vivo Fitness Costs of Different Gag CD8 T-Cell Escape Mutant Simian-Human Immunodeficiency Viruses for Macaques

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