Displaying publications 1 - 20 of 205 in total

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  1. Nakashima Y, Inoue E, Inoue-Murayama M, Abd Sukor JR
    Oecologia, 2010 Nov;164(3):721-30.
    PMID: 20602116 DOI: 10.1007/s00442-010-1714-1
    Many carnivorous mammals consume fruits and disperse the intact seeds to specific sites. Few studies have attempted to quantify this seed dispersal or evaluate its effectiveness, despite its potential importance and functional uniqueness. In the study reported here, we found that a frugivorous carnivore, the common palm civet (Paradoxurus hermaphroditus), generated seed shadows that are distinct from those of the sympatric frugivore, the pig-tailed macaque (Macaca nemestrina), and played a unique and important role in the regeneration of Leea aculeata (Leeaceae). We found that macaques dispersed the seeds randomly, while civets dispersed them non-randomly to sites such as the banks of small rivers, rain-flow paths, abandoned trails, and treefall gaps, which are characterized by low stem density and canopy cover. Seeds of L. aculeata that were dispersed by civets to the banks of rivers and gaps had significantly higher survival and growth rates than those dispersed to rain-flow paths or abandoned trails. Seeds dispersed by macaques or to random locations also had low survival. Although the effects of the civets on seed fate were not straightforward, compared with macaques and random dispersal, civets significantly enhanced the survival and growth of L. aculeata seeds after 1 year. These results indicate that non-random dispersal by civets is important for the persistence of L. aculeata. Civets may disperse other plant species and thus could have profound effects on forest dynamics.
    Matched MeSH terms: Macaca nemestrina/physiology*
  2. Braima KA, Sum JS, Ghazali AR, Muslimin M, Jeffery J, Lee WC, et al.
    PLoS One, 2013;8(10):e77924.
    PMID: 24194901 DOI: 10.1371/journal.pone.0077924
    BACKGROUND: The suburban transmission of malaria in Selangor, Malaysia's most developed and populous state still remains a concern for public health in this region. Despite much successful control efforts directed at its reduction, sporadic cases, mostly brought in by foreigners have continued to occur. In addition, cases of simian malaria caused by Plasmodium knowlesi, some with fatal outcome have caused grave concern to health workers. The aim of this study was to investigate the possibility of local malaria transmission in suburban regions of Selangor, which are adjacent to secondary rainforests.

    FINDINGS: A malaria survey spanning 7 years (2006 - 2012) was conducted in Selangor. A total of 1623 laboratory confirmed malaria cases were reported from Selangor's nine districts. While 72.6% of these cases (1178/1623) were attributed to imported malaria (cases originating from other countries), 25.5% (414/1623) were local cases and 1.9% (31/1623) were considered as relapse and unclassified cases combined. In this study, the most prevalent infection was P. vivax (1239 cases, prevalence 76.3%) followed by P. falciparum (211, 13.0%), P. knowlesi (75, 4.6%), P. malariae (71, 4.4%) and P. ovale (1, 0.06%). Mixed infections comprising of P. vivax and P. falciparum were confirmed (26, 1.6%). Entomological surveys targeting the residences of malaria patients' showed that the most commonly trapped Anopheles species was An. maculatus. No oocysts or sporozoites were found in the An. maculatus collected. Nevertheless, the possibility of An. maculatus being the malaria vector in the investigated locations was high due to its persistent occurrence in these areas.

    CONCLUSIONS: Malaria cases reported in this study were mostly imported cases. However the co-existence of local cases and potential Plasmodium spp. vectors should be cause for concern. The results of this survey reflect the need of maintaining closely monitored malaria control programs and continuous extensive malaria surveillance in Peninsula Malaysia.

    Matched MeSH terms: Macaca fascicularis*
  3. Lekko YM, Che-Amat A, Ooi PT, Omar S, Mohd-Hamdan DT, Linazah LS, et al.
    J Vet Med Sci, 2021 Oct 31;83(11):1702-1707.
    PMID: 34544936 DOI: 10.1292/jvms.21-0144
    Tuberculosis (TB) is a chronic inflammatory and zoonotic disease caused by Mycobacterium tuberculosis complex (MTBC) members, affecting several domestic animals, wildlife species and humans. The preliminary investigation was aimed to detect antibody against MTBC among indigenous wildlife which are free-ranged wild boar, free-ranged wild macaques and captive Asian elephants in selected areas of Selangor and elephant conservation centre in Pahang, respectively. The results indicate that MTBC serodetection rate in wild boar was 16.7% (7.3-33.5 at 95% confidence interval (CI)) using an in-house ELISA bPPD IgG and 10% (3.5-25.6 at 95% CI) by DPP®VetTB assay, while the wild macaques and Asian elephant were seronegative. The univariate analysis indicates no statistically significant difference in risk factors for sex and age of wild boar but there was a significant positive correlation (P<0.05) between bovine TB in dairy cattle and wild boar seropositivity in the Sepang district.
    Matched MeSH terms: Macaca
  4. Rovie-Ryan JJ, Khan FAA, Abdullah MT
    BMC Ecol Evol, 2021 02 15;21(1):26.
    PMID: 33588750 DOI: 10.1186/s12862-021-01757-1
    BACKGROUND: We analyzed a combined segment (2032-bp) of the sex-determining region and the testis-specific protein of the Y-chromosome (Y-DNA) gene to clarify the gene flow and phylogenetic relationships of the long-tailed macaques (Macaca fascicularis) in Southeast Asia. Phylogenetic relationships were constructed using the maximum likelihood, Bayesian inference, and the median-joining network from a total of 164 adult male M. fascicularis from 62 localities in Malaysia, including sequences from the other regions from previous studies.

    RESULTS: Based on Y-DNA, we confirm the presence of two lineages of M. fascicularis: the Indochinese and Sundaic lineages. The Indochinese lineage is represented by M. fascicularis located northwards of the Surat Thani-Krabi depression region and is introgressed by the Macaca mulatta Y-DNA. The Sundaic lineage is free from such hybridization event, thus defined as the original carrier of the M. fascicularis Y-DNA. We further revealed that the Sundaic lineage differentiated into two forms: the insular and the continental forms. The insular form, which represents the ancestral form of M. fascicularis, consists of two haplotypes: a single homogenous haplotype occupying the island of Borneo, Philippines, and southern Sumatra; and the Javan haplotype. The more diverse continental form consists of 17 haplotypes in which a dominant haplotype was shared by individuals from southern Thai Peninsular (south of Surat Thani-Krabi depression), Peninsular Malaysia, and Sumatra. Uniquely, Sumatra contains both the continental and insular Y-DNA which can be explained by a secondary contact hypothesis.

    CONCLUSIONS: Overall, the findings in this study are important: (1) to help authority particularly in Malaysia on the population management activities including translocation and culling of conflict M. fascicularis, (2) to identify the unknown origin of captive M. fascicularis used in biomedical research, and; (3) the separation between the continental and insular forms warrants for the treatment as separate management units.

    Matched MeSH terms: Macaca fascicularis*
  5. Razzak MA, Hamid SB, Ali ME
    PMID: 26437367 DOI: 10.1080/19440049.2015.1087060
    Food forgery has posed considerable risk to public health, religious rituals, personal budget and wildlife. Pig, dog, cat, rat and monkey meat are restricted in most religions, but their sporadic adulteration are rampant. Market controllers need a low-cost but reliable technique to track and trace suspected species in the food chain. Considering the need, here we documented a lab-on-a-chip-based multiplex polymerase chain reaction (PCR) assay for the authentication of five non-halal meat species in foods. Using species-specific primers, 172, 163, 141, 129 and 108-bp sites of mitochondrial ND5, ATPase 6 and cytochrome b genes were amplified to detect cat, dog, pig, monkey and rat species under complex matrices. Species-specificity was authenticated against 20 different species with the potential to be used in food. The targets were stable under extreme sterilisation (121°C at 45 psi for 2.5 h) which severely degrades DNA. The assay was optimised under the backgrounds of various commercial meat products and validated for the analysis of meatballs, burgers and frankfurters, which are popular fast food items across the globe. The assay was tested to detect 0.1% suspected meats under commercial backgrounds of marketed foods. Instead of simplex PCR which detects only one species at a time, such a multiplex platform can reduce cost by at least fivefolds by detecting five different species in a single assay platform.
    Matched MeSH terms: Macaca fascicularis
  6. Ee Uli J, Yong CSY, Yeap SK, Rovie-Ryan JJ, Mat Isa N, Tan SG, et al.
    PeerJ, 2017;5:e3566.
    PMID: 28828235 DOI: 10.7717/peerj.3566
    The cynomolgus macaque (Macaca fascicularis) is an extensively utilised nonhuman primate model for biomedical research due to its biological, behavioural, and genetic similarities to humans. Genomic information of cynomolgus macaque is vital for research in various fields; however, there is presently a shortage of genomic information on the Malaysian cynomolgus macaque. This study aimed to sequence, assemble, annotate, and profile the Peninsular Malaysian cynomolgus macaque transcriptome derived from three tissues (lymph node, spleen, and thymus) using RNA sequencing (RNA-Seq) technology. A total of 174,208,078 paired end 70 base pair sequencing reads were obtained from the Illumina Hi-Seq 2500 sequencer. The overall mapping percentage of the sequencing reads to the M. fascicularis reference genome ranged from 53-63%. Categorisation of expressed genes to Gene Ontology (GO) and KEGG pathway categories revealed that GO terms with the highest number of associated expressed genes include Cellular process, Catalytic activity, and Cell part, while for pathway categorisation, the majority of expressed genes in lymph node, spleen, and thymus fall under the Global overview and maps pathway category, while 266, 221, and 138 genes from lymph node, spleen, and thymus were respectively enriched in the Immune system category. Enriched Immune system pathways include Platelet activation pathway, Antigen processing and presentation, B cell receptor signalling pathway, and Intestinal immune network for IgA production. Differential gene expression analysis among the three tissues revealed 574 differentially expressed genes (DEG) between lymph and spleen, 5402 DEGs between lymph and thymus, and 7008 DEGs between spleen and thymus. Venn diagram analysis of expressed genes revealed a total of 2,630, 253, and 279 tissue-specific genes respectively for lymph node, spleen, and thymus tissues. This is the first time the lymph node, spleen, and thymus transcriptome of the Peninsular Malaysian cynomolgus macaque have been sequenced via RNA-Seq. Novel transcriptomic data will further enrich the present M. fascicularis genomic database and provide future research potentials, including novel transcript discovery, comparative studies, and molecular markers development.
    Matched MeSH terms: Macaca fascicularis
  7. Rashid NR, Ali ME, Hamid SB, Rahman MM, Razzak MA, Asing, et al.
    PMID: 25906074 DOI: 10.1080/19440049.2015.1039073
    Being the third-largest primate population has not made macaque (Macaca fascicularis sp.) monkeys less exposed to threats and dangers. Despite wildlife protection, they have been widely hunted and consumed in several countries because of their purported nutritional values. In addition to trading as pure bush meats in several places, monkey meat has been sold in meatball and soup products in Indonesia. Thus the possibility of macaque meat trafficking under the label of common meats is quite high. This paper reports the development of a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with the shortest amplicon length for the confirmed detection of monkey meat under compromised states which are known to degrade DNA. We amplified a 120-bp region of d-loop gene using a pair of macaque-specific primers and confirmed their specificity for the target species through cross-challenging against 17 different species using a 141-bp site of an 18 S rRNA gene as an endogenous control for eukaryotes. This eliminated the possibilities of any false-negative detection with complex matrices or degraded specimens. The detection limit was 0.00001 ng DNA in a pure state and 0.1% of meat in mixed matrices and commercial meatball products. RFLP analysis further authenticated the originality of the PCR product and distinctive restriction patterns were found upon AluI and CViKI-1 digestion. A micro-fluidic lab-on-a-chip automated electrophoretic system separated the fragments with high resolution. The assay was validated for screening commercial meatball products with sufficient internal control.
    Matched MeSH terms: Macaca
  8. Sulaiman NA, Osman K, Hamzah NH, Amir SP
    Malays J Pathol, 2014 Apr;36(1):33-9.
    PMID: 24763233 MyJurnal
    Deaths due to blunt force trauma to the head as a result of assault are some of the most common cases encountered by the practicing forensic pathologist. Previous studies have shown inflicting injury to the head region is one of the most effective methods of murder. The important factors that determine severity of trauma include the type of weapon used, type and site of skull fracture, intracranial haemorrhage and severity of brain injury. The aim of this study was to determine the characteristics of blunt force trauma to the skull produced by different instruments. Nine adult monkeys (Macaca fascicularis) skulls were used as models. Commonly found blunt objects comprising of Warrington hammer, hockey stick and open face helmet were used in this study. A machine calibrated force generator was used to hold the blunt object in place and to hit the skulls at forces of 12.5N and 25N. Resultant traumatic effects and fractures (linear, depressed, basilar, comminuted, and distastic) were analyzed according to type of blunt object used; surface area of contact and absolute force (N/cm(2)) delivered. Results showed that all investigated instruments were capable of producing similar injuries. The severity of trauma was not related to the surface area of contact with the blunt objects. However, only high absolute forces produced comminuted fractures. These findings were observational, as the samples were too small for statistical conclusions.
    Matched MeSH terms: Macaca fascicularis
  9. Tan CW, Wittwer K, Lim XF, Uehara A, Mani S, Wang LF, et al.
    Emerg Microbes Infect, 2019;8(1):787-795.
    PMID: 31132935 DOI: 10.1080/22221751.2019.1621668
    Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.
    Matched MeSH terms: Macaca fascicularis
  10. Fong MY, Lau YL, Chang PY, Anthony CN
    Parasit Vectors, 2014;7:161.
    PMID: 24693997 DOI: 10.1186/1756-3305-7-161
    The monkey malaria parasite Plasmodium knowlesi is now recognized as the fifth species of Plasmodium that can cause human malaria. Like the region II of the Duffy binding protein of P. vivax (PvDBPII), the region II of the P. knowlesi Duffy binding protein (PkDBPαII) plays an essential role in the parasite's invasion into the host's erythrocyte. Numerous polymorphism studies have been carried out on PvDBPII, but none has been reported on PkDBPαII. In this study, the genetic diversity, haplotyes and allele groups of PkDBPαII of P. knowlesi clinical isolates from Peninsular Malaysia were investigated.
    Matched MeSH terms: Macaca fascicularis
  11. Leong YK, Awang A
    Microbiol. Immunol., 1990;34(2):153-62.
    PMID: 2161071
    Rotaviral infections in cynomolgus monkeys (Macaca fasicularis) were studied to ascertain its suitability as a model of infection and diarrhea caused by group A human rotaviruses. Formula-fed monkeys were used as they could be observed closely. Experimental rotaviral infection of cynomolgus monkeys was age-dependent; only young monkeys were readily infected. Formula-fed newborns were readily infected with cell-culture-adapted human (WA) and simian (SA11) viruses and with a rotavirus from a human fecal specimen. However, diarrhea was detected only in very young animals. A number of rotaviral shedding patterns as a function of time were observed. Although there was no typical viral shedding pattern which represented exclusive association of viral infection with diarrhea, the initial level of viral excretion and the maximum level of viral shedding attained were much higher in animals with diarrhea. Seroconversion occurred in less than half of the inoculated animals. The presence of maternal rotaviral antibodies did not prevent infection or diarrhea.
    Matched MeSH terms: Macaca*; Macaca fascicularis*
  12. Cheah PS, Norhani M, Bariah MA, Myint M, Lye MS, Azian AL
    Cornea, 2008 May;27(4):461-70.
    PMID: 18434851 DOI: 10.1097/ICO.0b013e318165642c
    To investigate the histological changes in primate cornea induced by short-term overnight orthokeratology (OK).
    Matched MeSH terms: Macaca fascicularis
  13. Sirskyj D, Weltzin R, Golshani A, Anderson D, Bozic J, Diaz-Mitoma F, et al.
    J Virol Methods, 2010 Feb;163(2):459-64.
    PMID: 19913054 DOI: 10.1016/j.jviromet.2009.11.014
    Several critical factors of an influenza microneutralization assay, utilizing a rapid biotin-streptavidin conjugated system for detecting influenza virus subtypes A and B, are addressed within this manuscript. Factors such as incubation times, amount of virus, cell seeding, sonication, and TPCK trypsin were evaluated for their ability to affect influenza virus neutralization in a microplate-based neutralization assay using Madin-Darby canine kidney (MDCK) cells. It is apparent that the amount of virus used in the assay is the most critical factor to be optimized in an influenza microneutralization assay. Results indicate that 100xTCID(50) of influenza A/Solomon Islands/03/2006 (H1N1) virus overloads the assay and results in no, to low, neutralization, in both ferret and macaque sera, respectively, whereas using 6xTCID(50) resulted in significantly improved neutralization. Conversely, strong neutralization was observed against 100xTCID(50) of B/Malaysia/2506/04 virus. In this manuscript the critical factors described above were optimized and the results indicate that the described biotin-streptavidin conjugated influenza microneutralization assay is a rapid and robust method for detecting the presence of functional, influenza virus-neutralizing antibodies.
    Matched MeSH terms: Macaca mulatta
  14. Balzamo E
    PMID: 7323374
    Out of a group of 12 M. nemestrina (originating from Malaysia), 9 adults had shown clinical signs induced by ILS at 25 c/sec. Six of them (3 males, 3 females) were very photosensitive; however, only 2 presented eyelid and/or head jerks after the end of ILS (level 4), but never a generalized seizure. Tactile periorbital stimuli favoured myoclonus. In all but the two of level 4, the intensity of clinical signs varied from one day to the next. In all implanted adult macaques, spontaneous paroxysmal EEG activities were seen during slow sleep in mostly anterior areas, but also during waking and REM sleep in some of them; however, their occurrence depended upon the individual and were not in all cases related to their level of photosensitivity. During ILS, paroxysmal discharges (spikes and waves and/or polyspikes and waves), isolated or in bursts at 3-4/sec were bilateral and symmetrical. They started in fronto-rolandic regions, then became generalized. This observation constitutes a new fact since the discovery, in 1966, of the photomyoclonic syndrome of Papio papio, Macaca nemestrina being another species of subhuman primates with a marked predisposition to photosensitive epilepsy.
    Matched MeSH terms: Macaca/physiology*; Macaca nemestrina/physiology*
  15. Galinski MR, Barnwell JW
    Trends Parasitol, 2009 May;25(5):200-4.
    PMID: 19345613 DOI: 10.1016/j.pt.2009.02.002
    Four human deaths caused by Plasmodium knowlesi, a simian malaria species, are stimulating a surge of public health interest and clinical vigilance in vulnerable areas of Southeast Asia. We, and other colleagues, emphasize that these cases, identified in Malaysia, are a clear warning that health facilities and clinicians must rethink the diagnosis and treatment of malaria cases presumed to be caused by a less virulent human malaria species, Plasmodium malariae.
    Matched MeSH terms: Macaca fascicularis/parasitology
  16. Ahmad A, Ahmad AH, Dieng H, Satho T, Ahmad H, Aziz AT, et al.
    J Med Entomol, 2011 Nov;48(6):1236-46.
    PMID: 22238885
    There is accumulating evidence that criminals wrap dead bodies in an attempt to conceal evidence. To anticipate the forensic implications of this phenomenon, we examined whether flies that are naturally associated with cadavers exhibit a delay in attendance or differ in species composition and abundance patterns because of the presence of wrapping material. Wrapped and exposed carcasses of dead monkeys placed in an oil plantation in Kedah, Malaysia, were visited over 50 d. On daily visits to each of the six carcasses, visiting adult flies were sampled using hand nets. Flies of 12 families were encountered. Calliphoridae (Chrysomya rufifacies Macquart and C. megacephala (F.) was the most prevalent family, followed by Sphaeroceridae. Some families tended to be more abundant in WRCs (i.e., Calliphoridae, Muscidae, and Phoridae), whereas others (i.e., Piophilidae, Sepsidae, and Psychodidae) were more prevalent in exposed carcasses. Wrapping delayed the arrival of all fly species encountered, with delays varying from 1 to 13 d depending on species. Wrapping did not affect species composition of flies, but prolong the occurrence of some species. The results of the current study emphasize the need to take into consideration the presence of a wrap when estimating postmortem interval.
    Matched MeSH terms: Macaca fascicularis
  17. Hickey AC, Koster JA, Thalmann CM, Hardcastle K, Tio PH, Cardosa MJ, et al.
    Am J Trop Med Hyg, 2013 Dec;89(6):1043-57.
    PMID: 24062475 DOI: 10.4269/ajtmh.13-0145
    Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.
    Matched MeSH terms: Macaca mulatta
  18. Färnert A, Bronner U
    Lakartidningen, 2009 May-Jun;106(21-22):1465-9.
    PMID: 19579434
    Matched MeSH terms: Macaca fascicularis/parasitology
  19. Benavente ED, Gomes AR, De Silva JR, Grigg M, Walker H, Barber BE, et al.
    Sci Rep, 2019 07 08;9(1):9873.
    PMID: 31285495 DOI: 10.1038/s41598-019-46398-z
    The zoonotic Plasmodium knowlesi parasite is the most common cause of human malaria in Malaysia. Genetic analysis has shown that the parasites are divided into three subpopulations according to their geographic origin (Peninsular or Borneo) and, in Borneo, their macaque host (Macaca fascicularis or M. nemestrina). Whilst evidence suggests that genetic exchange events have occurred between the two Borneo subpopulations, the picture is unclear in less studied Peninsular strains. One difficulty is that P. knowlesi infected individuals tend to present with low parasitaemia leading to samples with insufficient DNA for whole genome sequencing. Here, using a parasite selective whole genome amplification approach on unprocessed blood samples, we were able to analyse recent genomes sourced from both Peninsular Malaysia and Borneo. The analysis provides evidence that recombination events are present in the Peninsular Malaysia parasite subpopulation, which have acquired fragments of the M. nemestrina associated subpopulation genotype, including the DBPβ and NBPXa erythrocyte invasion genes. The NBPXb invasion gene has also been exchanged within the macaque host-associated subpopulations of Malaysian Borneo. Our work provides strong evidence that exchange events are far more ubiquitous than expected and should be taken into consideration when studying the highly complex P. knowlesi population structure.
    Matched MeSH terms: Macaca fascicularis/parasitology
  20. Lim PY, Hickey AC, Jamiluddin MF, Hamid S, Kramer J, Santos R, et al.
    Vaccine, 2015 Nov 4;33(44):6017-24.
    PMID: 26271825 DOI: 10.1016/j.vaccine.2015.05.108
    A vaccine against human enterovirus 71 (EV-A71) is urgently needed to combat outbreaks of EV-A71 and in particular, the serious neurological complications that manifest during these outbreaks. In this study, an EV-A71 virus-like-particle (VLP) based on a B5 subgenogroup (EV-A71-B5 VLP) was generated using an insect cell/baculovirus platform. Biochemical analysis demonstrated that the purified VLP had a highly native procapsid structure and initial studies in vivo demonstrated that the VLPs were immunogenic in mice. The impact of VLP immunization on infection was examined in non-human primates using a VLP prime-boost strategy prior to EV-A71 challenge. Rhesus macaques were immunized on day 0 and day 21 with VLPs (100 μg/dose) containing adjuvant or with adjuvant alone (controls), and were challenged with EV-A71 on day 42. Complete blood counts, serum chemistry, magnetic resonance imaging (MRI) scans, and histopathology results were mostly normal in vaccinated and control animals after virus challenge demonstrating that the fatal EV-A71-B3 clinical isolate used in this study was not highly virulent in rhesus macaques. Viral genome and/or infectious virus were detected in blood, spleen or brain of two of three control animals, but not in any specimens from the vaccinated animals, indicating that VLP immunization prevented systemic spread of EV-A71 in rhesus macaques. High levels of IgM and IgG were detected in VLP-vaccinated animals and these responses were highly specific for EV-A71 particles and capsid proteins. Serum from vaccinated animals also exhibited similar neutralizing activity against different subgenogroups of EV-A71 demonstrating that the VLPs induced cross-neutralizing antibodies. In conclusion, our EV-A71-B5 VLP is safe, highly immunogenic, and prevents systemic EV-A71-B3 infection in nonhuman primates making it a viable attractive vaccine candidate for EV-A71.
    Matched MeSH terms: Macaca mulatta
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