Comparison of immunity generated by nucleic acid-, MF59-, and ISCOM-formulated human immunodeficiency virus type 1 vaccines in Rhesus macaques: evidence for viral clearance

The kinetics of T-helper immune responses generated in 16 mature outbred rhesus monkeys (Macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune responses to monomeric recombinant gp120SF2 (rgp120) when the protein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by incorporation into immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2 protein-immunized groups, but the responses showed different kinetics, while NA were delayed and their levels were low in the DNA-immunized animals. Antigen-specific gamma interferon (IFN-gamma) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN-gamma and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-gamma (type 1-like), and IL-4 responses that peaked after the second immunization. To determine which type of immune responses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 construct. Protection was observed in the two groups receiving the rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely protected from infection. In other subunit vaccinees there was evidence by multiple assays that virus detected at 2 weeks postchallenge was effectively cleared. Early induction of potent type 1- as well as type 2-like T-helper responses induced the most-effective immunity.     

Immunogenetic studies of maternal-fetal relationships: a review: why newborn rhesus monkeys don't get hemolytic disease

The discovery of the Rh blood group factor in humans was made using the red blood cells of rhesus monkeys. Because of its importance to human medicine and immunogenetics, this finding contributed greatly to the appreciation of the importance of nonhuman primates in research. It is now widely recognized that blood group incompatibility between mother and fetus can lead to differential fertility, fetal death, and hemolytic disease of the newborn (HDN).The blood group systems of several nonhuman primate species have been studied in detail and found to be analogous, although not identical, to those of humans. It is therefore surprising that HDN has been reported in only four nonhuman primate species-marmosets, sacred baboons, chimpanzees, and orangutans. Maternal-fetal blood group incompatibility and its consequences have been extensively studied in rhesus monkeys, and these macaques may well be representative of many nonhuman primates. Rhesus monkeys exhibit all five of the conditions that lead to HDN in humans: (1) blood group incompatible matings: (2) transplacental hemorrhage: (3) maternal immunization to blood group alloantigens on fetal erythrocytes: (4) transplacental transfer of maternal antibodies; and (5) coating of the newborn's erythrocytes. Yet, newborns show no clinical or hematological evidence of HDN.We have shown that the rhesus alloantibodies engendered by transplacental immunization do not mediate immune elimination of the newborn's erythrocytes. Evaluation of the maternal antibodies demonstrated that they have low titers and low avidities and perhaps belong to IgG subclasses that do not bind effectively to receptors on phagocytic cells of the rhesus reticuloendothelial system. The newborn's genotype may also affect the expression of allogeneic blood group antigens and thereby help protect the newborn's cells from destruction. These factors together undoubtedly play a major role in the survival of the antibody-coated newborn's RBC and are thus able to account for the absence of HDN in this species.     

Tetanus antibody titers and duration of immunity to clinical tetanus infections in free-ranging rhesus monkeys (Macaca mulatta)

Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2-year-old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two-dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long-term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long-term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great.     

Incidence of Maternal Rh Immunization by ABO Compatible and Incompatible Pregnancies

The incidence of maternal Rh immunization in Rh-negative women following a single ABO compatible Rh-positive pregnancy is about 17%. This incidence was determined by following Rh-negative women through two Rh-incompatible pregnancies and analysing their sera for anti-Rh at the time of delivery of their second observed pregnancy. Maternal Rh immunization occurs almost exclusively after delivery; however, antibodies may not be detectable in the absence of further antigenic stimulation.The incidence of maternal Rh immunization when maternal-foetal ABO incompatibility is also present is 9–13% and 17% for group O and non-group O women respectively. This study emphasizes the need to offer Rh-immune prophylaxis to Rh-negative women having Rh-positive infants whether or not ABO incompatibility exists between the mother and infant.     

Experience with vaccine prophylaxis of hepatitis B among different groups of children

The immunological activity of different vaccines against hepatitis B was evaluated in the Hepatological Center organized on the basis of the Infectious Hospital in Tula. Newborn infants were immunized with the use of the following vaccines: Engerix B (Belgium), Combiotech (Russia), Euvax B (Aventis Pastèur, South Korea). Altogether, after the full course of immunization anti-HBs were detected in 76 children out of 81 (in 93.8%). Vaccine Engerix B, when introduced according to the schedule 0-1-2-12 months, exhibited high immunogenic properties in a group of infants born of women with persistent HBs-antigenemia. Anti-HBs at a concentration exceeding 1000 I.U./I could be detected in 84.6%. In another group of children immunized according to the schedule 0-1-6 months first with vaccine Combiotech at the age of 0 and 1 month, then (at the age of 6 months) with vaccine Euvax, the presence of postvaccinal anti HBs at protective concentration was registered in all children. After immunization against hepatitis B with the use of all above-mentioned vaccines introduced according to both schedules high immunological activity and safety of immunization were noted.     

AdHu5Ag85A Respiratory Mucosal Boost Immunization Enhances Protection against Pulmonary Tuberculosis in BCG-Primed Non-Human Primates

Persisting high global tuberculosis (TB) morbidity and mortality and poor efficacy of BCG vaccine emphasizes an urgent need for developing effective novel boost vaccination strategies following parenteral BCG priming in humans. Most of the current lead TB vaccine candidates in the global pipeline were developed for parenteral route of immunization. Compelling evidence indicates respiratory mucosal delivery of vaccine to be the most effective way to induce robust local mucosal protective immunity against pulmonary TB. However, despite ample supporting evidence from various animal models, there has been a lack of evidence supporting the safety and protective efficacy of respiratory mucosal TB vaccination in non-human primates (NHP) and humans. By using a rhesus macaque TB model we have evaluated the safety and protective efficacy of a recombinant human serotype 5 adenovirus-based TB vaccine (AdHu5Ag85A) delivered via the respiratory mucosal route. We show that mucosal AdHu5Ag85A boost immunization was safe and well tolerated in parenteral BCG-primed rhesus macaques. A single AdHu5Ag85A mucosal boost immunization in BCG-primed rhesus macaques enhanced the antigen–specific T cell responses. Boost immunization significantly improved the survival and bacterial control following M.tb challenge. Furthermore, TB-related lung pathology and clinical outcomes were lessened in BCG-primed, mucosally boosted animals compared to control animals. Thus, for the first time we show that a single respiratory mucosal boost immunization with a novel TB vaccine enhances protection against pulmonary TB in parenteral BCG-primed NHP. Our study provides the evidence for the protective potential of AdHu5Ag85A as a respiratory mucosal boost TB vaccine for human application.     

Immune response of rhesus macaques to recombinant simian immunodeficiency virus gp130 does not protect from challenge infection.

Simian immunodeficiency virus (SIV) infection of rhesus macaques is a model for human immunodeficiency virus (HIV) infection in humans. Inactivated and modified live whole-virus vaccines have provided limited protective immunity against SIV in rhesus macaques. Because of safety concerns in the use of inactivated and live whole-virus vaccines, we evaluated the protective immunity of vaccinia virus recombinants expressing the surface glycoprotein (gp130) of SIVmac and subunit preparations of gp130 expressed in mammalian cells (CHO). Three groups of animals were immunized with recombinant SIV gp130. The first group received SIV gp130 purified from genetically engineered CHO cells (cSIVgp130), the second group was vaccinated with recombinant vaccinia virus expressing SIVmac gp130 (vSIVgp130), and the third group was first primed with vSIVgp130 and then given a booster immunization with cSIVgp130. Although anti-gp130 binding antibodies were elicited in all three groups, neutralizing antibodies were transient or undetectable. None of the immunized animals resisted intravenous challenge with a low dose of cell-free virus. However, the group primed with vSIVgp130 and then boosted with cSIVgp130 had the lowest antigen load (p27) compared with the other groups. The results of these studies suggest that immunization of humans with HIV type 1 surface glycoprotein may not provide protective immunity against virus infection.     

Modulation of antigen-specific humoral responses in rhesus macaques by using cytokine cDNAs as DNA vaccine adjuvants

An important limitation of DNA immunization in nonhuman primates is the difficulty in generating high levels of antigen-specific antibody responses; strategies to enhance the level of immune responses to DNA immunization may be important in the further development of this vaccine strategy for humans. We approached this issue by testing the ability of molecular adjuvants to enhance the levels of immune responses generated by multicomponent DNA vaccines in rhesus macaques. Rhesus macaques were coimmunized intramuscularly with expression plasmids bearing genes encoding Th1 (interleukin 2 [IL-2] and gamma interferon)- or Th2 (IL-4)-type cytokines and DNA vaccine constructs encoding human immunodeficiency virus Env and Rev and simian immunodeficiency virus Gag and Pol proteins. We observed that the cytokine gene adjuvants (especially IL-2 and IL-4) significantly enhanced antigen-specific humoral immune responses in the rhesus macaque model. These results support the assumption that antigen-specific responses can be engineered to a higher and presumably more desirable level in rhesus macaques by genetic adjuvants.     

多囊卵巢综合征猕猴的生殖特性(英文)

多囊卵巢综合征(PCOS)是临床上常见的一种内分泌失调性疾病,也是造成无排卵性不孕的重要原因。对多囊卵巢综合征动物模型的研究有10余年,迄今尚未建立起较为理想的模型动物。该研究的目的在于构建猕猴多囊卵巢综合征动物模型,并分析该模型动物的一些主要生殖特性。将6只成年雌性猕猴(6～10a)平均分成2组:PCOS模型组和对照组。模型组动物的建立方法是:在月经周期的第1、3、5天,分别皮下注射丙酸睾丸酮一次,剂量为3.5mg/kg体重;接着在第7、9、11天,分别肌注人绒毛膜促性腺激素一次,剂量是350IU/kg体重;连续注射2个月经周期。对照组动物注射生理盐水。结果显示:PCOS模型组动物呈现出高血清LH和T,分别为(5.35±0.17)IU/L和(7.58±0.14)ng/mL,而且血清LH/FSH值(5.35/1.30=4.12);模型组动物血清FSH、E2和P的含量与对照组无显著差异。腹部B超扫描结果提示,模型组动物卵巢多囊化。对两组动物进行超排处理后,模型组动物卵巢呈明显的过刺激现象,模型组动物胚胎体外培养的囊胚率为23.53%,显著低于对照组(66.67%)(P<0.05),即用丙酸睾丸酮联合人绒毛膜促性腺激素,能够建立PCOS猕猴模型,该模型动物的一些主要生殖特性与人类PCOS相似。     

Priming of human papillomavirus type 11-specific humoral and cellular immune responses in college-aged women with a virus-like particle vaccine

In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] = 28.4; 95% confidence interval [CI] = 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer = 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-gamma) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-gamma production and significantly correlated with IL-2 production after the third immunization (P = 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre- and postimmunization.     

An immuno-haematological study among pregnant women of Patiala (India).

The present study has been conducted on 500 pregnant women belonging to Patiala city (Punjab State, India), during various stages of pregnancy, who were investigated for evidence of immunization. Incidence of immunization was found to be 1.20% in total sample and 25.00% in Rh (D) negative pregnant women. All the immunized cases were multiparae. Immunized cases were more in second trimester. Obstetrical histories of immunized cases suggest that five of them were probably immunized due to repeated pregnancies and one case was probably due to previous still births. A greater fertility was observed in the immunized group as compared to other groups. No case of immunization had previous history of blood transfusion. Rh-immunization was also studied in relation to AB0-incompatibility.     

Immunogenetic studies of rhesus monkeys

To assay for transplacental immunization in rhesus monkeys, sera from 253 postpartum females, 31 virgin females, and 40 males were tested for erythrocyte agglutinins. Nineteen percent of the mothers exhibited antibodies, but less than three percent of the virgin females or males did so. Antibodies were detected in 26 percent of the mothers who bore blood group-incompatible infants, in contrast to only eight percent of the mothers with compatible offspring. Thus, blood group incompatibility may lead to transplacental alloimmunization of the rhesus female. Unlike the situation in humans, hemolytic disease was not observed, even when the erythrocytes of the newborn rhesus were coated with maternal antibodies.     

Reduction of peak viremia by an integration-defective SIV proviral DNA vaccine in rhesus macaques

An integrase-defective SIV (idSIV) vaccine delivered by a DNA prime and viral particle boost approach can suppress viral loads (VLs) during the acute infection stage after intravenous SIVmac239 challenge. This study investigated how idSIV DNA and viral particle immunization alone contributed to the suppression of VLs in Chinese rhesus macaques after SIV challenge. Two macaques were immunized with idSIV DNA five times and two macaques were immunized with idSIV viral particles three times. Cellular and humoral immune responses were measured in the vaccinated macaques after immunization. The VLs and CD4⁺ T cell counts were monitored for 28 weeks after the intravenous SIVmac239 challenge. The SIV-specific T cell responses were only detected in the DNA-vaccinated macaques. However, binding and neutralizing antibodies against autologous and heterologous viruses were moderately better in macaques immunized with viral particles than in macaques immunized with DNA. After the challenge, the mean peak viremia in the DNA group was 2.3 logs lower than that in the control group, while they were similar between the viral particle immunization and control groups. Similar CD4⁺ T cell counts were observed among all groups. These results suggest that idSIV DNA immunization alone reduces VLs during acute infection after SIV challenge in macaques and may serve as a key component in combination with other immunogens as prophylactic vaccines.     

Strategies to Improve Child Immunization via Antenatal Care Visits in India: A Propensity Score Matching Analysis

Numerous studies have examined the empirical evidence concerning the influence of demographic and socio-economic factors influencing child immunization, but no documentation is available which shows the actual impact of antenatal care (ANC) visits on subsequent child immunization. Therefore, this paper aims to examine the net impact of ANC visits on subsequent utilization of child immunization after removing the presence of selection bias. Nationwide data from India’s latest National Family Health Survey conducted during 2005–06 is used for the present study. The analysis has been carried out in the two separate models, in the first model 1–2 ANC visit and in the second model three or more ANC visits has been compared with no visit. We have used propensity score matching method with a counterfactual model that assesses the actual ANC visits effect on treated (ANC visits) and untreated groups (no ANC visit), and have employed Mantel-Haenszel bounds to examine whether result would be free from hidden bias or not. Using matched sample analysis result shows that child immunization among the groups of women who have completed 1–2 ANC visits and those who had more than two visits was about 13 percent and 19 percent respectively, higher than the group of women who have not made any ANC visit. Findings of nearest neighbor matching with replacement method, which completely eliminated the bias, indicate that selection bias present in data set leads to overestimates the positive effects of ANC visits on child immunization. Result based on Mantel-Haenszel bounds method suggest that if around 19 percent bias would be involved in the result then also we could observe the true positive effect of 1–2 ANC visits on child immunization. This also indicates that antenatal clinics are the conventional platforms for educating pregnant women on the benefits of child immunization.     

The human-ABO blood groups of free-ranging long-tailed macaques (Macaca fascicularis) and parapatric rhesus macaques (M. mulatta) in Thailand

BACKGROUND: Long-tailed and rhesus macaques are widely used in biomedical research; therefore, the known blood group is important. METHODS: The human-type ABO blood group was determined in wild or semi-wild long-tailed and rhesus macaques in Thailand. A total of 729 long-tailed and 160 rhesus macaques from 20 localities were temporarily caught. RESULTS: The frequency profiles of blood groups, calculated by averaging the frequency of each troop in long-tailed and rhesus macaques, were AB > O > B > A at 29.6%, 27.4%, 27.2%, and 15.8%, and B > AB > A > O at 39.6%, 33.4%, 18.2%, and 8.8%, respectively. Irrespective of locality, the frequencies were AB > O > B > A of 29.6%, 28.0%, 24.4%, and 18.0%, and AB > B > A > O of 37.5%, 28.7%, 26.9%, and 6.9%, respectively, for all long-tailed and rhesus macaques. The frequency profile of blood groups in Thai rhesus macaques was somewhat similar to that in the parapatric long-tailed macaques; however, it was different from other rhesus populations where only group B was detected. CONCLUSIONS: Our data support the hypothesis that Indochinese rhesus macaques are hybrids between rhesus and long-tailed macaques in the past.     

Protective Efficacy of a Single Immunization of a Chimeric Adenovirus Vector-Based Vaccine against Simian Immunodeficiency Virus Challenge in Rhesus Monkeys

Rare serotype and chimeric recombinant adenovirus (rAd) vectors that evade anti-Ad5 immunity are currently being evaluated as potential vaccine vectors for human immunodeficiency virus type 1 and other pathogens. We have recently reported that a heterologous rAd prime-boost regimen expressing simian immunodeficiency virus (SIV) Gag afforded durable partial immune control of an SIV challenge in rhesus monkeys. However, single-shot immunization may ultimately be preferable for global vaccine delivery. We therefore evaluated the immunogenicity and protective efficacy of a single immunization of chimeric rAd5 hexon hypervariable region 48 (rAd5HVR48) vectors expressing SIV Gag, Pol, Nef, and Env against a homologous SIV challenge in rhesus monkeys. Inclusion of Env resulted in improved control of peak and set point SIV RNA levels following challenge. In contrast, DNA vaccine priming did not further improve the protective efficacy of rAd5HVR48 vectors in this system.Heterologous prime-boost vaccine regimens have proven substantially more immunogenic than single vector immunizations in a variety of experimental models, but a single-shot vaccine would presumably be ideal for eventual global delivery. The potential utility of single-shot vaccines against pathogenic simian immunodeficiency virus (SIV) challenges in rhesus monkeys has not been well characterized. We therefore evaluated the protective efficacy of a single immunization of recombinant chimeric adenovirus type 5 (rAd5) hexon hypervariable region 48 (rAd5HVR48) vectors (15) expressing SIV Gag, Pol, Nef, and Env against a pathogenic SIV challenge in rhesus monkeys. These vectors contain the HVRs of the rare Ad48 serotype and have been shown to evade dominant Ad5 hexon-specific neutralizing antibodies (NAbs) (15). We also assessed the potential utility of inclusion of Env as an immunogen (6, 7, 17) and the degree to which DNA vaccine priming would enhance the protective efficacy afforded by a single rAd5HVR48 immunization (2, 7, 18, 21).Thirty adult rhesus monkeys (n = 6/group) lacking the Mamu-A*01, Mamu-B*17, and Mamu-B*08 class I alleles were primed with plasmid DNA vaccines and boosted with rAd5HVR48 vectors as follows: (1) adjuvanted DNA prime, rAd5HVR48 boost; (2) DNA prime, rAd5HVR48 boost; (3) rAd5HVR48 alone; (4) rAd5HVR48 alone (excluding Env); and (5) sham controls. Monkeys in groups 1 to 3 received vectors expressing SIVmac239 Gag, Pol, Nef, and Env, whereas monkeys in group 4 received vectors expressing only Gag, Pol, and Nef. The DNA vaccine adjuvants in group 1 were plasmids expressing the rhesus chemokine MIP-1α and Flt3L, which have been shown to increase recruitment of dendritic cells and to improve DNA vaccine immunogenicity (20). Monkeys were primed intramuscularly with a total dose of 4 mg of DNA vaccines at weeks 0, 4, and 8. All animals then received a single intramuscular immunization of 4 × 10¹⁰ viral particles (vp) of rAd5HVR48 at week 24. At week 52, animals were challenged intravenously (i.v.) with 100 monkey infectious doses of SIVmac251 (7, 10).     

以恒河猴为模型的DNA疫苗的免疫保护作用研究

研究了以霍乱毒素B亚基（CTB）为载体的重组疟疾多价抗原（AWTE）表位的DNA疫苗在恒河猴中的免疫原性及对相应疟原虫感染的免疫保护作用。结果表明DNA疫苗组免疫2次后即产生了较高水平的细胞免疫和体液免疫,免疫后91天用1.25×10     

Design and analysis of rhesus cytomegalovirus IL-10 mutants as a model for novel vaccines against human cytomegalovirus

Background

Human cytomegalovirus (HCMV) expresses a viral ortholog (CMVIL-10) of human cellular interleukin-10 (cIL-10). Despite only ∼26% amino acid sequence identity, CMVIL-10 exhibits comparable immunosuppressive activity with cIL-10, attenuates HCMV antiviral immune responses, and contributes to lifelong persistence within infected hosts. The low sequence identity between CMVIL-10 and cIL-10 suggests vaccination with CMVIL-10 may generate antibodies that specifically neutralize CMVIL-10 biological activity, but not the cellular cytokine, cIL-10. However, immunization with functional CMVIL-10 might be detrimental to the host because of its immunosuppressive properties.

Methods and Findings

Structural biology was used to engineer biologically inactive mutants of CMVIL-10 that would, upon vaccination, elicit a potent immune response to the wild-type viral cytokine. To test the designed proteins, the mutations were incorporated into the rhesus cytomegalovirus (RhCMV) ortholog of CMVIL-10 (RhCMVIL-10) and used to vaccinate RhCMV-infected rhesus macaques. Immunization with the inactive RhCMVIL-10 mutants stimulated antibodies against wild-type RhCMVIL-10 that neutralized its biological activity, but did not cross-react with rhesus cellular IL-10.

Conclusion

This study demonstrates an immunization strategy to neutralize RhCMVIL-10 biological activity using non-functional RhCMVIL-10 antigens. The results provide the methodology for targeting CMVIL-10 in vaccine, and therapeutic strategies, to nullify HCMV''s ability to (1) skew innate and adaptive immunity, (2) disseminate from the site of primary mucosal infection, and (3) establish a lifelong persistent infection.     

Morphological and Body Color Variation in Thai <Emphasis Type="Italic">Macaca fascicularis fascicularis</Emphasis> North and South of the Isthmus of Kra

Long-tailed macaques (Macaca fascicularis fascicularis) are widely distributed in Southeast Asia and are morphologically and genetically (Tosi et al. in International Journal of Primatology 23:161–178, 2002) distinguishable on either side of the Isthmus of Kra (ca. 10.5°N). We compared the somatometry and body color of 15 local populations of long-tailed macaques in Thailand distributed over areas from 6.5°N to 16.3°N and also a Thai rhesus macaque population at 17.2°N. Limb proportions and body color variation follow the geographical trend. However, contrary to a previous report, body size does not decrease with latitude in the northern group and also in the southern (southerly distributed) rhesus macaque. Relative tail length (RTL) and color contrast in yellow between the back and thigh are the sole traits that distinctively separate the 2 groups: the southern group has a long relative tail length (RTL >125%) and small color contrast, whereas the northern group has a short RTL (<120%) and large color contrast. The southern rhesus macaques appear to have somatometric and body color traits that follow the geographical trend in long-tailed macaques, though they maintain their distinctive species-specific traits of shorter RTL (ca. 55%), shorter relative facial length, and a bipartite body color pattern. Researchers assume that the northern group of long-tailed macaques and the southern rhesus macaques had undergone partial introgression with each other. Montane refugia present during the glacial period are localities in which introgression occurred in long-tailed macaques.     

恒河猴piwil4基因的鉴定与表达分析

为了研究人类近亲恒河猴中PIWI家族蛋白PIWIL4的结构和表达情况,文章首次利用同源比对和RT-PCR方法克隆了恒河猴piwil4基因,检测了其mRNA在恒河猴心脏、脑、结肠、附睾和睾丸5种组织中的表达情况,利用生物信息学的方法对恒河猴piwil4基因和人的PIWIL4(HIWI2)基因编码的蛋白产物进行了同源性分析和结构域分析,并进一步利用免疫组化的方法比较了PIWIL4蛋白在成人、成年恒河猴和性未成熟恒河猴睾丸组织中的表达分布。结果表明,恒河猴piwil4 mRNA在多组织中表达,恒河猴和人的PIWIL4蛋白的氨基酸序列同源性达97%以上,均含有PAZ和Piwi结构域,它们在两物种成年个体睾丸组织中空间分布一致,但在不同发育阶段恒河猴睾丸组织中的分布发生了改变,幼猴中PIWIL4蛋白主要表达于生精小管细胞的细胞核,在成年猴睾丸组织中则表达于各种细胞的胞浆中。上述结果提示,piwil4基因在人类和恒河猴精子发生过程中作用类似,PIWIL4蛋白在幼猴和成年猴睾丸组织中的表达差异提示它们在不同发育阶段功能的改变。