The immune dominant repetitive epitope of the circumsporozoite protein of Plasmodium falciparum was fused to the pre-S2 region of the surface antigen of hepatitis B virus within an expression cassette. Yeast cells transformed with vectors carrying the fusions synthesized hybrid proteins that assembled into particles similar to those formed in human serum from the surface antigen alone. These hybrid protein particles expose the circumsporozoite epitope on their exterior and induce a high titer antibody response towards the circumsporozoite epitope in immunized animals. The antibodies show typical circumsporozoite precipitin reactions and inhibit invasion of hepatoma cells in vitro, both indicative of a protective immune response. This formulation could prove useful as a candidate sporozoite malaria vaccine for human clinical trials.
Two representative cases of subarachnoid hemorrhage in which prostaglandin D2 (PGD2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), stable metabolite of prostacyclin (PGI2), were monitored with serial lumbar punctures and detected in cisternal CSF during operations for aneurysm, are reported. In the case with demonstrated arterial vasospasm, prostaglandin D2 has a concentration trend with characteristic peak related to vasospasm; the synthesis of prostacyclin appears inhibited after the hemorrhage. In the patient without radiologic evidence of vasospasm, arachidonate metabolite concentration trend appears in a steady-state. Cisternal prostaglandin D2 concentration in the patient with demonstrated vasospasm is two times the highest lumbar CSF concentration, while 6-keto-prostaglandin F1 alpha concentration is very low. This suggests the role of the clotting phenomenon and likely confirms the importance of arachidonate metabolites in the genesis of cerebral arterial spasm following subarachnoid hemorrhage.
Two antigens, cholera toxin (CT) and a synthetic albumin-conjugated 16-residue peptide derived from the circumsporozoite (CS) protein of Plasmodium falciparum sporozoites, were tested as immunogens in rabbits. The malaria peptide-albumin conjugate by itself was completely nonimmunogenic, and although cholera toxin was immunogenic it also expressed considerable native toxicity. After attachment of CT to liposomes containing ganglioside GM1, toxicity of CT was completely eliminated and antigenicity was enhanced. Therefore liposomes may be capable of reducing toxicity of certain potentially dangerous antigens such as toxins. After incorporation of the malaria peptide-albumin conjugate into liposomes a high titre of specific antibodies was induced against the malaria peptide but not against albumin. These antibodies also reacted with native CS protein. Three adjuvants, including lipid A and two types of lipophilic muramyl dipeptide, were compared and found to be effective in liposomes. Based both on the conversion of synthetic P. falciparum CS peptide from a nonimmunogenic to an immunogenic form and on the ‘toxoiding’ effect of liposomes for CT, it is concluded that liposomes should be considered as being a useful carrier for antigens and adjuvants for vaccines for poorly antigenic or toxic substances.
Journal Article Disposable nitrocellulose filtration plates simplify the Dot-ELISA for serodiagnosis of visceral leishmaniasis Get access Ian McGregor, Ian McGregor President Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael G. Pappas, Michael G. Pappas Dept. of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Ruta Hajkowski, Ruta Hajkowski Dept. of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Carter L. Diggs, Carter L. Diggs Dept. of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Wayne T. Hockmeyer Wayne T. Hockmeyer Dept. of Immunology, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Washington, D.C. 20307, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 79, Issue 1, 1985, Page 136, https://doi.org/10.1016/0035-9203(85)90261-5 Published: 01 January 1985 Article history Accepted: 23 August 1984 Published: 01 January 1985
Abstract : This program sought to develop an effective, practical vaccine against African trypanosomiasis, useful to both military and civilian agencies. Related benefits include acquisition of knowledge pertaining to trypanosome immunity, host response and pathology of infection. Experiments conducted at WRAIR and in Kenya have demonstrated that experimental animals can be successfully immunized with irradiated trypanosomes. Rodents, cattle and monkeys can be rendered completely resistant to a challenging infection of T. rhodesiense. Partial immunity has been achieved against T. congolense. Continuing studies in Lambwe Valley, Western Kenya, show that 18 of 31 and 21 of 29 isolates from humans over a 7-year period are neutralized by two antisera, respectively. Five of 27 isolates from bovines also were neutralized by one antiserum. This indicates that stability of antigenic types has persisted throughout this period and that cattle are a reservoir host in the valley. Complete resistence to T. congolense has been achieved by repeated infection and cure. This immunity appears to be maintained after both syringe and tsetse fly challenge.
A study was conducted to determine the feasibility of measuring blood meal volume in Aedes aegypti using a radioisotope blood label in lieu of weight differentials. This mosquito species defaecated numerous droplets of a clear fluid beginning while blood feeding was in progress and continuing for up to 3 hr post-feeding. Excretion of this clear fluid occurred regardless of the age or prior nutritional conditioning of the mosquito. When mosquitoes were fed on blood labeled with Ce-144, this radioisotope remained completely with the blood meal and was not passed in the clear excreta. When blood meal volumes were estimated using the radioisotope method, significantly greater values were obtained compared to those calculated by the classical weighing method. A direct relationship was demonstrated between blood meal volume and the quantity of clear fluid excreted. Consequently, the error inherent in the weighing method was increased in mosquitoes taking large blood meals. Ce-144 did not label red blood cells but remained in the plasma. The radioisotope was completely expelled with the blood meal excreta.