Malaria vaccine

Summary Among infectious diseases caused by protozoa, malaria is still the greatest killer of children. Mortality in adults living in endemic areas is significantly lower because they frequently acquire partial or complete immunity to the major pathogen,Plasmodium falciparum. This natural protection indicates that vaccination may be possible, and the first candidate antigens were cloned with the use of human immune sera as probes. Genetic and biochemical analysis of the parasite proteins revealed that they are polymorphic, and frequently gene sequences were discovered which were specific for a particular parasite isolate, which eliminated most antigens for purposes of vaccine development. The most promising candidate antigens today are the major surface proteins of sporozoites and blood stage parasites. However, the immune response against those is not sufficient for complete protection, and additional, intensive research is necessary to identify new molecules to be included in a vaccine cocktail against malaria. The current spread of the disease due to increasing drug resistance of parasites and mosquito vectors emphasizes the urgent need for a vaccine.     

Malaria prophylaxis in travellers: The current position

Summary Malaria prevention is a main challenge for physicians, nurses, health officers and tour operators. The attack rate of malaria in travellers is 1–10/10,000 departures, and the case fatality rate of imported malaria is around 0.5/100. Travellers should be informed about the risk they are going to take, how to protect against mosquito bites, about the antimalarials they will have to take and about what to do when a malaria breakthrough should occur.The 4-aminoquinolines (chloroquine, amodiaquine) remain the drug of choice for the prevention ofPlasmodium vivax and of sensitiveP. falciparum infections. The problem is to find an effective and safe drug combination for travellers to areas whereP. falciparum is either resistant to chloroquine, to Fansidar (the combination of pyrimethamine plus sulfadoxine) or to both. These travellers will probably best be protected by an individually tailored drug combination, which includes amodiaquine or mefloquine as baseline drugs, and a supplementation with Fansidar, Maloprim (the combination of pyrimethamine with dapsone), paludrine or an antibiotic.     

疟疾子孢子疫苗的研究进展

本文系统地回顾了疟疾疫苗的发展史,将疫苗研究的发展分为与生物技术的发展密切相关的三个时期;重点阐述了疟疾子孢子疫苗在不同时期的研究进展,并分析了疟疾疫苗研究的现状和面临的困难。     

Our impasse in developing a malaria vaccine

Malaria presents a challenge to world health that to date has been beyond the abilities of researchers to conquer. This critique presents some of the strategies employed by the parasite to overcome immunity and the immunological challenges that we face to develop vaccines. A conclusion is that a vaccine must identify novel antigens or epitopes that are not normally immunogenic and which are therefore not under immune pressure and most likely to be conserved between different strains. Such antigens are most likely to be targets of cellular immunity. The case for a whole parasite blood stage vaccine is presented based on these premises.     

Large-scale purification of inactivated influenza vaccine using membrane molecular filtration

Summary A procedure is reported for the elimination of at least 95% of hens' egg protein impurities from inactivated influenza vaccine, by selective molecular filtration through a membrane with a cut-off limit of 1×10⁶ daltons.     

Inhibition of epinephrine-induced glycogen phosphorylase activation byBordetella pertussis vaccine in rats

Zusammenfassung Die Glycogen-Phosphorylase-aktivierende Wirkung von Epinephrin wurde in Lebern und Muskeln von Ratten durch BPV-Behandlung gehemmt und die Epinephrinempfindlichkeit der BPV-behandelten Tiere durch Prednisolon wiederhergestellt.     

In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine

Summary Monocytes, obtained from a human volunteer immunized with aLeishmania infantum-derived vaccine, when cultured in vitro displayed a strong parasiticidal activity againstL. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal unexposed donors, and to murine macrophages.     

In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine

Monocytes, obtained from a human volunteer immunized with a Leishmania infantum-derived vaccine, when cultured in vitro displayed a strong parasiticidal activity against L. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal, unexposed donors, and to murine macrophages.     

Interaction ofBordetella pertussis vaccine treatment and lymphocytic choriomeningitis virus infection in mice

Zusammenfassung Gleichzeitig verabreichteBordetella pertussis Vakzine und lymphozytäre Choriomeningitis Virus bewirkt keine Splenomegalie und auch keine lymphozytäre Choriomeningitis.     

Surface antigens of Plasmodium falciparum-infected erythrocytes as immune targets and malaria vaccine candidates

Understanding the targets and mechanisms of human immunity to malaria caused by Plasmodium falciparum is crucial for advancing effective vaccines and developing tools for measuring immunity and exposure in populations. Acquired immunity to malaria predominantly targets the blood stage of infection when merozoites of Plasmodium spp. infect erythrocytes and replicate within them. During the intra-erythrocytic development of P. falciparum, numerous parasite-derived antigens are expressed on the surface of infected erythrocytes (IEs). These antigens enable P. falciparum-IEs to adhere in the vasculature and accumulate in multiple organs, which is a key process in the pathogenesis of disease. IE surface antigens, often referred to as variant surface antigens, are important targets of acquired protective immunity and include PfEMP1, RIFIN, STEVOR and SURFIN. These antigens are highly polymorphic and encoded by multigene families, which generate substantial antigenic diversity to mediate immune evasion. The most important immune target appears to be PfEMP1, which is a major ligand for vascular adhesion and sequestration of IEs. Studies are beginning to identify specific variants of PfEMP1 linked to disease pathogenesis that may be suitable for vaccine development, but overcoming antigenic diversity in PfEMP1 remains a major challenge. Much less is known about other surface antigens, or antigens on the surface of gametocyte-IEs, the effector mechanisms that mediate immunity, and how immunity is acquired and maintained over time; these are important topics for future research.     

Experimental myocarditis: Enhancement by the use of pertussis vaccine in Lewis rats

Zusammenfassung Nachweis, dass Pertussis Impfstoff die Neigung zur Entstehung experimenteller Myokarditis bei Inzucht-Lewis-Ratten, die mit Kaninchen- und Rattenherzextrakten in vollständig Freund'schem Adjuvans immunisiert wurden, verstärkt. Keine zunehmende Neigung zur Entwicklung der Krankheit wurde hingegen festgestellt, wenn wahllos gezÜchtete, genetisch nicht verwandte Ratten (Hebrew University strain «Sabra») in derselben Weise behandelt wurden.

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Supported by a research grant from the Hebrew University and Hadassah Medical Orginazition, and by grant No. HE-05739 from the National Institutes of Health, U.S.P.H.S., Bethesda (Md., USA).     

The use of cyclophosphamide as an enhancer of the vaccine against foot-and-mouth disease

The immunization of biungulate animals with killed foot-and-mouth disease virus (FMDV) requires periodic vaccinations due to a low vaccine immunogenicity. Therefore, FMDV antigens need to be combined with adjuvants such as aluminum hydroxide, saponin or oil emulsions. Animal handling for periodic inoculations, and the repeated doses of vaccines that have to be administered increase the commercialization costs. Moreover, the use of adjuvants may induce adverse effects.In the present work we show that it is possible to increase the life span of neutralizing antibodies in serum when a single dose of cyclophosphamide (Cy) is administered four days before vaccination with aluminum hydroxidesaponin FMDV vaccine.     

Immunoglobulin-binding proteins in ticks: new target for vaccine development against a blood-feeding parasite

Humans have a long history of trying to control ticks. At first, attempts focused on modifying the habitat, whereas later efforts relied heavily on the use of chemicals. Current research is directed at finding a vaccine against ticks. A strategy of targeting 'concealed antigens' succeeded with the first commercialised vaccine against the cattle tick Boophilus microplus. However, vaccine development against other tick species appears unsatisfactory to date. Vaccination depends on a specific antibody-mediated immunoreaction that damages the parasite. Immunoglobulin molecules of vertebrate hosts can pass through gut barriers into the haemolymph of ectoparasites while retaining antibody activity. Research on the ixodid tick Rhipicephalus appendiculatus revealed that host immunoglobulin-G in the parasite was excreted via salivation, during feeding. Immunoglobulin-binding proteins in tick haemolymph and salivary glands are thought to be responsible for such excretion. The discovery of an immunoglobulin excretion system in ticks indicates that they have a highly developed mechanism to protect themselves from their host's antibody attack. Such a mechanism questions whether immunization strategies will be effective against ticks, unless they circumvent or disable the ticks' immunoglobulin excretion system.     

Hematopoietic changes in NMRI mice after the intravenous and subcutaneous injection ofBordetella pertussis vaccine

Zusammenfassung Sowohl die i.v. als auch die s.c. Injektion abgetöteter Zellen vonBordetella pertussis führt bei Mäusen zu Splenomegalie und ausgeprägter Blut-Leukozytose, an der Lymphozyten und Granulozyten beteiligt sind. Zudem bewirkte die Injektion vonB. pertussis eine deutliche Verminderung der Erythrocyten mit Minimalwerten am 5. Tag. Am 10. Tag und danach wurden wieder Normalwerte gefunden.

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This study was supported by the Kurt- und Inge-Schuster-Stiftung.