Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Sullivan JS[original query] |
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Protective efficacy of a Plasmodium vivax circumsporozoite protein-based vaccine in Aotus nancymaae is associated with antibodies to the repeat region
Yadava A , Hall CE , Sullivan JS , Nace D , Williams T , Collins WE , Ockenhouse CF , Barnwell JW . PLoS Negl Trop Dis 2014 8 (10) e3268 We have previously reported that Vivax Malaria Protein 001 (VMP001), a vaccine candidate based on the circumsporozoite protein of Plasmodium vivax, is immunogenic in mice and rhesus monkeys in the presence of various adjuvants. In the present study, we evaluated the immunogenicity and efficacy of VMP001 formulated with a TLR9 agonist in a water-in-oil emulsion. Following immunization, the vaccine efficacy was assessed by challenging Aotus nancymaae monkeys with P. vivax sporozoites. Monkeys from both the low- and high-dose vaccine groups generated strong humoral immune responses to the vaccine (peak median titers of 291,622), and its subunits (peak median titers to the N-term, central repeat and C-term regions of 22,188; 66,120 and 179,947, respectively). 66.7% of vaccinated monkeys demonstrated sterile protection following challenge. Protection was associated with antibodies directed against the central repeat region. The protected monkeys had a median anti-repeat titer of 97,841 compared to 14,822 in the non-protected monkeys. This is the first report demonstrating P. vivax CSP vaccine-induced protection of Aotus monkeys challenged with P. vivax sporozoites. |
Schistosoma mansoni infection impairs anti-malaria treatment and immune responses in mosquito-borne Plasmodium coatneyi infected rhesus macaques
Semenya AA , Sullivan JS , Barnwell JW , Secor WE . Infect Immun 2012 80 (11) 3821-7 Malaria and schistosomiasis are the world's two most important parasitic infections in terms of distribution, morbidity and mortality. In areas where Plasmodium and Schistosoma species are both endemic, co-infections are commonplace. Mouse models demonstrate that schistosomaisis worsens a malaria infection; however, just as mice and humans differ greatly, the murine infecting Plasmodium species differ as much from those that infect humans. Research into human co-infections (S. haemotobium-P. falciparum versus S. mansoni-P. falciparum) has produced conflicting results. The rhesus macaque model provides a helpful tool for understanding the role of S. mansoni on malaria parasitemia and anti-malarial immune responses using P. coatneyi, a malaria species that closely resembles P. falciparum infection in humans. Eight rhesus macaques were exposed to S. mansoni cercariae. Eight weeks later, these animals plus 8 additional macaques were exposed to malaria either through bites of infected mosquitos or intravenous inoculation. When malaria infection was initiated from mosquito bites, co-infected animals displayed increased malaria parasitemia, decreased hematocrit levels, and suppressed malaria specific antibody responses compared to malaria infection alone. However, macaques infected by intravenous inoculation with erythrocytic stage parasites did not display these same differences in parasitemia, hematocrit or antibody responses between the two groups. Use of the macaque model provides information that begins to unravel differences in pathological and immunological outcomes observed between humans with P. falciparum that are co-infected with S. mansoni or S. haematobium. Our results suggest that migration of malaria parasites through livers harboring schistosome eggs may alter host immune responses and infection outcomes. |
Mosquito infection studies with Aotus monkeys and humans infected with the Chesson strain of Plasmodiun vivax
Collins WE , Sullivan JS , Jeffery GM , Nace D , Williams T , Galland GG , Williams A , Barnwell JW . Am J Trop Med Hyg 2012 86 (3) 398-402 Oocyst counts were compared between mosquitoes that fed on humans versus mosquitoes that fed on Aotus monkeys, both of which were infected with the Chesson strain of Plasmodium vivax. Oocyst counts obtained from mosquitoes fed on humans were almost 10-fold higher in number. Mosquitoes were more likely to be infected and with a higher rate of infection when they fed on monkeys before the peak in the asexual parasite count. Mosquitoes that fed on humans were more likely to be more heavily infected when fed after the peak in the asexual count. Of several species of owl monkeys, Aotus vociferans was infected at a higher frequency. On the basis of oocyst counts, Anopheles dirus were the most susceptible and An. maculatus were the least susceptible of the mosquito species tested. |
A New World primate deficient in tetherin-mediated restriction of human immunodeficiency virus type 1
Wong SK , Connole M , Sullivan JS , Choe H , Carville A , Farzan M . J Virol 2009 83 (17) 8771-80 Human immunodeficiency virus type 1 (HIV-1) does not replicate in primary cells of New World primates. To better understand this restriction, we expressed owl monkey (Aotus nancymaae) CD4 and CXCR4 in the owl monkey kidney cell line, OMK. An HIV-1 variant modified to evade the owl monkey restriction factor TRIM-cyp replicated efficiently in these cells but could not replicate in primary A. nancymaae CD4-positive T cells. To understand this difference, we examined APOBEC3G and tetherin orthologs from OMK cells and primary A. nancymaae cells. We observed that OMK cells expressed substantially lower levels of APOBEC3G than did A. nancymaae cells. A. nancymaae, but not marmoset (Callithrix jacchus), APOBEC3G was partially downregulated by HIV-1 vif and reduced but did not abolish HIV-1 replication when stably expressed in OMK cells. The functional difference between A. nancymaae and marmoset APOBEC3Gs mapped to residue 128, previously shown to distinguish African green monkey from human APOBEC3G. We also characterized tetherin orthologs from OMK and A. nancymaae cells. The A. nancymaae tetherin ortholog, but not OMK tetherin, prevented HIV-1 release. Alteration of threonine 181 of OMK tetherin rescued its function and its efficient N glycosylation. All alleles of Aotus lemurinus griseimembra examined, but none of A. nancymaae or Aotus vociferans, encoded this nonfunctional tetherin ortholog. Our data indicate that HIV-1 replication in owl monkeys is not restricted at entry but can be limited by APOBEC3G and tetherin. Further, A. lemurinus griseimembra does not restrict HIV-1 replication via tetherin, a property likely useful for the study of tetherin-restricted viruses. |
Infection of mosquitoes with Plasmodium falciparum by feeding on humans and on Aotus monkeys
Collins WE , Jeffery GM , Sullivan JS , Nace D , Williams T , Galland GG , Williams A , Barnwell JW . Am J Trop Med Hyg 2009 81 (3) 529-33 Of 1,004 positive lots of mosquitoes fed on 229 humans infected with Plasmodium falciparum, 46.2% had 1-10 oocysts/(+)gut, 21.2% had 10-30 oocysts/(+)gut, 22.2% had 30-100 oocysts/(+)gut, and 10.4% had > 100 oocysts/(+) gut. The highest levels of infection occurred between 6 and 15 days after the peak in the asexual parasite count. Of 2,281 lots of Anopheles freeborni mosquitoes fed on splenectomized Aotus monkeys infected with the Santa Lucia strain of P. falciparum, 1,191 were infected (52.2%). The highest intensity infections ranged from 2.78 oocysts per positive gut in mosquitoes fed on Aotus vociferans to 6.08 oocysts per positive gut for those fed on A. lemurinus griseimembra to 10.4 oocysts per positive gut for those fed on A. nancymaae. The pattern of infection for mosquitoes fed on splenectomized Aotus monkeys was similar to that obtained by feeding on humans, but the intensity, based on oocyst/(+)gut, was much lower. |
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