The Effects of Oral Lavender Therapy on Wounding in Chimpanzees (Pan troglodytes).

Lavender administration in humans has been shown to promote calmness without the side effects often observed with benzodiazepines. Studies in both humans and rodents have found that ingestion of oral lavender capsules resulted in significantly decreased anxiety. Additionally, mice developed an anti-conflict effect and humans increased socially inclusive behaviors. Given the safety of oral lavender oil and the observed benefits, we administered daily lavender capsules to six chimpanzees who exhibited conflict-instigating behaviors in an effort to further decrease our already low levels of wounding. We compared the total number of wounds in 25 chimpanzees housed with the six lavender-treated chimpanzees in five different social groups (1) prior to administration of daily oral lavender capsules to (2) total wounds during daily oral lavender capsule treatment. We hypothesized that lavender therapy treatment would reduce overall wounding in the social groups. Surprisingly, overall wounding was higher during the lavender treatment period (p = 0.01), yet the percentage of wounds requiring treatment significantly decreased during the lavender therapy period (36% vs. 21%, p = 0.02).

Corrigendum to "Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques".

[This corrects the article DOI: 10.1155/2010/860160.].

Malignant Neoplasia of the Sex Skin in 2 Chimpanzees (Pan troglodytes).

This report describes 2 cases of spontaneous malignant neoplasia within the sex skin of aged female chimpanzees. In both cases, the initial presentation resembled nonhealing traumatic wounds to the sex skin, with different degrees of infection, ulceration, and tissue necrosis. Histopathology of the lesions confirmed the diagnosis of squamous cell carcinoma in one case and of adenocarcinoma with metastasis in the other. Advanced age and previous trauma likely contributed to the development of the neoplasias in both cases; long-term sun exposure may also have contributed to the development of the squamous cell carcinoma. To our knowledge, these 2 cases represent the first reports of sex skin neoplasia in chimpanzees.

Use of an Implantable Loop Recorder in a Chimpanzee (Pan troglodytes) to Monitor Cardiac Arrhythmias and Assess the Effects of Acupuncture and Laser Therapy.

Cardiovascular disease is a leading cause of death in captive chimpanzees and is often associated with myocardial fibrosis, which increases the risk of cardiac arrhythmias. In this case report, we present a 36-y-old male chimpanzee (Pan troglodytes) diagnosed with frequent ventricular premature complexes (VPC). We placed a subcutaneous implantable loop recorder for continual ECG monitoring to assess his arrhythmias without the confounding effects of anesthetics. During his initial treatment with the antiarrhythmia medication amiodarone, he developed thrombocytopenia, and the drug was discontinued. After reviewing other potential therapies for the treatment of cardiac arrhythmias, we elected to try acupuncture and laser therapy in view of the positive results and the lack of adverse side effects reported in humans. We used 2 well-known cardiac acupuncture sites on the wrist, PC6 (pericardium 6) and HT7 (heart 7), and evaluated the results of the therapy by using the ECG recordings from the implantable loop recorder. Although periodic increases in the animal's excitement level introduced confounding variables that caused some variation in the data, acupuncture and laser therapy appeared to decrease the mean number of VPC/min in this chimpanzee.

Mural Dissections of Brain-Supplying Arteries in a Chimpanzee (Pan troglodytes).

We describe the pathologic features of mural arterial dissection involving brain-supplying arteries in a 31-y-old female chimpanzee (Pan troglodytes). Several hours after examination for a possible respiratory tract infection, the chimpanzee became unresponsive, developed seizures, and died within 18 h. At necropsy, the occipital cortex of the brain had a small area of congestion, and the cerebellar cortex contained a small necrotic area. Histologic evaluation confirmed the cortical lesions and revealed an additional necrotic area in the medulla oblongata characterized by mural dissection of the brain-supplying vertebral and basilar arteries and subsequent branches. Lesions in the cortices and medulla were within areas supplied by the vertebrobasilar system. Dissection of brain-supplying arteries has been described in humans but not previously in chimpanzees (or any other NHP), suggesting that these species might be useful in understanding this condition in humans. In addition, the lesion should be added to the NHP clinician's and pathologist's differential diagnosis list for similar presentations in this species.

Comparison of systemic and mucosal immunization with helper-dependent adenoviruses for vaccination against mucosal challenge with SHIV.

Most HIV-1 infections are thought to occur at mucosal surfaces during sexual contact. It has been hypothesized that vaccines delivered at mucosal surfaces may mediate better protection against HIV-1 than vaccines that are delivered systemically. To test this, rhesus macaques were vaccinated by intramuscular (i.m.) or intravaginal (ivag.) routes with helper-dependent adenoviral (HD-Ad) vectors expressing HIV-1 envelope. Macaques were first immunized intranasally with species C Ad serotype 5 (Ad5) prior to serotype-switching with species C HD-Ad6, Ad1, Ad5, and Ad2 vectors expressing env followed by rectal challenge with CCR5-tropic SHIV-SF162P3. Vaccination by the systemic route generated stronger systemic CD8 T cell responses in PBMC, but weaker mucosal responses. Conversely, mucosal immunization generated stronger CD4 T cell central memory (Tcm) responses in the colon. Intramuscular immunization generated higher levels of env-binding antibodies, but neither produced neutralizing or cytotoxic antibodies. After mucosal SHIV challenge, both groups controlled SHIV better than control animals. However, more animals in the ivag. group had lower viral set points than in in the i.m. group. These data suggest mucosal vaccination may have improve protection against sexually-transmitted HIV. These data also demonstrate that helper-dependent Ad vaccines can mediate robust vaccine responses in the face of prior immunity to Ad5 and during four rounds of adenovirus vaccination.

Acupuncture as an adjunct therapy for osteoarthritis in chimpanzees (Pan troglodytes).

Acupuncture is an ancient practice that is currently used to treat disorders ranging from osteoarthritis to cardiomyopathy. Acupuncture involves the insertion of thin, sterile needles into defined acupuncture points that stimulate physiologic processes through neural signaling. Numerous scientific studies have proven the benefits of acupuncture, and given this scientific support, we hypothesized that acupuncture could benefit the nonhuman primates at our facility. As our chimpanzee colony ages, we are observing an increase in osteoarthritis and have focused our initial acupuncture treatments on this condition. We successfully trained 3 chimpanzees, by using positive-reinforcement training techniques, to voluntarily participate in acupuncture treatments for stifle osteoarthritis. We used 3 acupuncture points that correlate with alleviation of stifle pain and inflammation in humans. A mobility scoring system was used to assess improvements in mobility as a function of the acupuncture treatments. The 2 chimpanzees with the most severe osteoarthritis showed significant improvement in mobility after acupuncture treatments. Acupuncture therapy not only resulted in improved mobility, but the training sessions also served as enrichment for the animals, as demonstrated by their voluntary participation in the training and treatment sessions. Acupuncture is an innovative treatment technique that our data show to be safe, inexpensive, and, most importantly, effective for chimpanzees.

Obstructive uropathy secondary to uterine leiomyoma in a chimpanzee (Pan troglodytes).

Complications due to uterine leiomyomata in chimpanzees have rarely been documented. Here we describe a female chimpanzee that developed severe hydronephrosis in the right kidney due to leiomyoma. Because hysterectomy did not alleviate the hydronephrosis, nephrectomy was elected. After these procedures, the chimpanzee is doing well. Leiomyomata screening programs with treatment algorithms are a useful component of a comprehensive chimpanzee program.

Functional impairment of central memory CD4 T cells is a potential early prognostic marker for changing viral load in SHIV-infected rhesus macaques.

In HIV infection there is a paucity of literature about the degree of immune dysfunction to potentially correlate and/or predict disease progression relative to CD4(+) T cells count or viral load. We assessed functional characteristics of memory T cells subsets as potential prognostic markers for changing viral loads and/or disease progression using the SHIV-infected rhesus macaque model. Relative to long-term non-progressors with low/undetectable viral loads, those with chronic plasma viremia, but clinically healthy, exhibited significantly lower numbers and functional impairment of CD4(+) T cells, but not CD8(+) T cells, in terms of IL-2 production by central memory subset in response to PMA and ionomycine (PMA+I) stimulation. Highly viremic animals showed impaired cytokine-production by all T cells subsets. These results suggest that functional impairment of CD4(+) T cells in general, and of central memory subset in particular, may be a potential indicator/predictor of chronic infection with immune dysfunction, which could be assayed relatively easily using non-specific PMA+I stimulation.

Prime-boost vaccination using chemokine-fused gp120 DNA and HIV envelope peptides activates both immediate and long-term memory cellular responses in rhesus macaques.

HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFgamma ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

Comparison of replication-competent, first generation, and helper-dependent adenoviral vaccines.

All studies using human serotype 5 Adenovirus (Ad) vectors must address two major obstacles: safety and the presence of pre-existing neutralizing antibodies. Helper-Dependent (HD) Ads have been proposed as alternative vectors for gene therapy and vaccine development because they have an improved safety profile. To evaluate the potential of HD-Ad vaccines, we compared replication-competent (RC), first-generation (FG) and HD vectors for their ability to induce immune responses in mice. We show that RC-Ad5 and HD-Ad5 vectors generate stronger immune responses than FG-Ad5 vectors. HD-Ad5 vectors gave lower side effects than RC or FG-Ad, producing lower levels of tissue damage and anti-Ad T cell responses. Also, HD vectors have the benefit of being packaged by all subgroup C serotype helper viruses. We found that HD serotypes 1, 2, 5, and 6 induce anti-HIV responses equivalently. By using these HD serotypes in heterologous succession we showed that HD vectors can be used to significantly boost anti-HIV immune responses in mice and in FG-Ad5-immune macaques. Since HD vectors have been show to have an increased safety profile, do not possess any Ad genes, can be packaged by multiple serotype helper viruses, and elicit strong anti-HIV immune responses, they warrant further investigation as alternatives to FG vectors as gene-based vaccines.

Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines.

Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helper-dependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5-immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination.

Oral immunization of rhesus macaques with adenoviral HIV vaccines using enteric-coated capsules.

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag and a string of six highly-conserved HIV-1 envelope peptides representing broadly cross-reactive CD4(+) and CD8(+) T cell epitopes. Oral immunization of rhesus macaques with these capsules primed antigen-specific mucosal and systemic immune responses and subsequent intranasal delivery of the envelope peptide cocktail using a mutant cholera toxin adjuvant boosted cellular immune responses including, antigen-specific intracellular IFN-gamma-producing CD4(+) and CD8(+) effector memory T cells in the intestine. These results suggest that the combination of oral adenoviral vector priming followed by intranasal protein/peptide boosting may be an effective mucosal HIV vaccination strategy for targeting viral antigens to the GI tract and priming systemic and mucosal immunity.