A Nonhuman Primate Model for Rectally Transmitted Syphilis

Tansey, Cassandra; Zhao, Chunxia; Hopkins, Andre; Ritter, Jana M.; Fakile, Yetunde; Pillay, Allan; Katz, Samantha S.; Pereira, Lara; Mitchell, James; Deyounks, Frank; Kersh, Ellen N.; McNicholl, Janet M.; Vishwanathan, Sundaram A.

doi:10.1093/infdis/jix669

Cited by 6 publications

(5 citation statements)

References 14 publications

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“…The STI infection status for C. trachomatis , T. vaginalis was monitored with the APTIMA Combo 2 assay (Hologic, San Diego, California, USA). Serum antibodies showing syphilis infections were determined using T. pallidum particle agglutination (TP-PA) and Rapid Plasma Reagin (RPR) assays as described before [ 17 ]. Pinch biopsies from suspected vaginal syphilitic lesions collected via colposcopy were fixed in 10% neutral buffered formalin.…”

Section: Methodsmentioning

confidence: 99%

“…In NHP models, DMPA increases risk of SIV [14] and SHIV [15] acquisition by thinning macaque vaginal epithelium, reducing its barrier function [15], increasing target cells, and altering mucosal pH and mucus properties [15,16]. Both models in this study recapitulate human STI, with discharge, ulcers, and T. pallidum seroconversion [12,13,17].…”

Section: Introductionmentioning

confidence: 99%

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Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques

Vishwanathan¹,

Zhao²,

Luthra³

et al. 2021

Aids

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Objective: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women. Design: Two macaque models of increasing vaginal STI severity were used for efficacy assessment. Methods: The first study ( n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis . Six animals were CAB-LA treated and five were controls. The second study ( n = 9) included a triple STI model with repeated exposures to C. trachomatis , T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time. Results: All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P < 0.001) or one challenge (log-rank P = 0.002), respectively. Both models recapitulated human STI disease, with vaginal discharge, ulcers, and seroconversion. Conclusion: In these high and sustained susceptibility models spanning more than 3 months, CAB-LA maintained complete efficacy, demonstrating robustness of the CAB-LA dose used in clinical trials, and suggesting its insensitivity to multiple STIs and DMPA.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques

Vishwanathan¹,

Zhao²,

Luthra³

et al. 2021

Aids

Self Cite

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“…non-human primates, hamsters, guinea pigs, and mice). While only non-human primates and rabbits develop clinical signs similar to humans ( 40 , 42 ), mice and other rodents may be useful to study bacteria dissemination ( 43 ).…”

Section: Treponema Pallidum Subsp Pallidummentioning

confidence: 99%

Syphilis vaccine: challenges, controversies and opportunities

et al. 2023

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Syphilis is a sexually or vertically (mother to fetus) transmitted disease caused by the infection of Treponema pallidum subspecie pallidum (TPA). The incidence of syphilis has increased over the past years despite the fact that this bacterium is an obligate human pathogen, the infection route is well known, and the disease can be successfully treated with penicillin. As complementary measures to preventive campaigns and early treatment of infected individuals, development of a syphilis vaccine may be crucial for controlling disease spread and/or severity, particularly in countries where the effectiveness of the aforementioned measures is limited. In the last century, several vaccine prototypes have been tested in preclinical studies, mainly in rabbits. While none of them provided protection against infection, some prototypes prevented bacteria from disseminating to distal organs, attenuated lesion development, and accelerated their healing. In spite of these promising results, there is still some controversy regarding the identification of vaccine candidates and the characteristics of a syphilis-protective immune response. In this review, we describe what is known about TPA immune response, and the main mechanisms used by this pathogen to evade it. Moreover, we emphasize the importance of integrating this knowledge, in conjunction with the characterization of outer membrane proteins (OMPs), to expedite the development of a syphilis vaccine that can protect against TPA infection.

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“…In this regard, models of vaginal Chlamydia trachomatis, Treponema pallidum, and SHIV could be used to determine if combinations of doxycycline and anti-HIV drugs can prevent vaginal infection with all three pathogens. The recent development of rectal Treponema pallidum and rectal Chlamydia trachomatis and lymphogranuloma venereum (LGV) models might help to investigate if doxycycline can prevent rectal infection of Chlamydia trachomatis, LGV, Treponema pallidum, and SHIV as part of an MPT [ 62 , 63 ]. Such studies may inform promising drug combinations, concentrations, and delivery routes and guide their clinical implementation.…”

Section: Macaque Modeling Of Preexposure Prophylaxis In the Setting O...mentioning

confidence: 99%

The predictive value of macaque models of preexposure prophylaxis for HIV prevention

Garcı́a-Lerma

McNicholl

Heneine

2022

Current Opinion in HIV and AIDS

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Purpose of reviewWe review macaque models for preexposure prophylaxis (PrEP) for HIV prevention and highlight their role in advancing currently approved and novel PrEP agents. Recent findingsThe development of the repeat low dose simian HIV (SHIV) challenge models represented a significant advancement in preclinical PrEP modeling that has allowed the investigation of PrEP under conditions that better mimic HIV exposures in humans. These models incorporate relevant drug pharmacology to inform drug correlates of PrEP protection. Models of rectal, vaginal, and penile infection are now available and have been found to predict clinical efficacy of all the currently approved PrEP strategies including daily oral PrEP with the combination of emtricitabine and tenofovir disoproxil fumarate or tenofovir alafenamide, and a long-acting formulation of the integrase inhibitor cabotegravir. These models are being used to test new PrEP modalities including the nucleoside reverse transcriptase-translocation inhibitor islatravir and longacting capsid inhibitors. The SHIV models have also been supplemented by sexually transmitted infection co-infections with Chlamydia trachomatis, Treponema pallidum or Trichomonas vaginalis to assess the impact of inflammation on PrEP efficacy.

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A Nonhuman Primate Model for Rectally Transmitted Syphilis

Cited by 6 publications

References 14 publications

Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques

Sexually transmitted infections and depot medroxyprogesterone acetate do not impact protection from simian HIV acquisition by long-acting cabotegravir in macaques

Syphilis vaccine: challenges, controversies and opportunities

The predictive value of macaque models of preexposure prophylaxis for HIV prevention

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