Passage of hemolysins through the midgut epithelium of femaleIxodes ricinus L. fed on rabbits infested or reinfested with ticks

Summary Antibodies considered in this study are hemolysins synthesized by rabbits against sheep red blood cells. Ingested with the blood meal, they cross the tick midgut epithelium and retain their immunological properties in the hemolymph. During a reinfestation of rabbits, more ticks present these antibodies, and titres are generally higher than during a first infestation. Hemolysins are only found in ticks weighing 180 mg or more.The present work was supported by the Swiss National Foundation for Scientific Research, grant No. 3070.81.     

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 vaccine

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.     

The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tick Amblyomma americanum.

Phosphodiesterase (PDE) activity in the salivary glands of the female. Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased when glands were stimulated with cyclic AMP and theophylline. Dopamine stimulated PDE activity and an 'inhibitory' factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.     

Comparison of cutaneous hyperemia in cattle elicited by larvae ofBoophilus microplus and by prostaglandins and other mediators

Summary Blood flow has been measured in bovine skin following the injection of tick antigens and a number of pharmacological mediators; including histamine, prostaglandins and slow reacting substance of anaphylaxis. The greates increase in blood flow (20 times normal) was recorded with tick antigens and with prostaglandin F2. This mediator may therefore influence blood flow during immune reactions to ticks and during the rapid ingestion of blood by the ticks.Acknowledgments. This work was supported by the Australian Meat Research Committee. We would like to thank J. M. Gough for her technical assistance.     

Modification of the skin feeding site by tick saliva mediates virus transmission.

A tick vector of Thogoto (THO) virus was shown to secrete a factor in saliva which potentiates the transmission of THO virus to uninfected ticks feeding on an apparently non-viraemic host. The effect of the saliva activated transmission (SAT) factor on the virus occurred at the site of inoculation in the skin and was apparent even when the virus was introduced 3 days after the SAT factor. The results suggest that tick saliva can play an important role in disease transmission by virtue of host modification at the site of feeding.     

Modification of the skin feeding site by tick saliva mediates virus transmission

A tick vector of Thogoto (THO) virus was shown to secrete a factor in saliva which potentiates the transmission of THO virus to uninfected ticks feeding on an apparently non-viraemic host. The effect of the saliva activated transmission (SAT) factor on the virus occurred at the site of inoculation in the skin and was apparent even when the virus was introduced 3 days after the SAT factor. The results suggest that tick saliva can play an important role in disease transmission by virtue of host modification at the site of feeding.     

Piroplasmal sporozoites in the Argasid Ornithodoros erraticus (Lucas)

Summary The infective forms of Nuttallia, meri, a small-mammal piroplasm, first appear as spindle-shaped sporozoites in and around the salivary glands of Ornithodoros erraticus (small race) 30 days after the ticks had fed on infected blood. O. erraticus is the only soft tick so far proved to transmit a piroplasm.I thank Miss Zipora Goldberg for meticulous technical help, Mrs H. Salomon for the photomicrographs, and Dr. Y. Schlein and Prof. P. C. C. Garnham, F. R. S. for advice and comments.     

Effect of host age on the expression of acquired resistance to ticks

Summary Young guinea-pigs (350 g) expressed significantly greater levels of acquired resistance to challenge by larvalAmblyomma americanum ticks than older guinea-pigs (520–800 g). This finding suggests that younger guinea-pigs are immunologically more responsive to tick infestation than older mature individuals. Therefore, host age is an important variable in evaluating acquired resistance to ticks.Supported in part by grants from the United States Public Health Service, National Institutes of Health No. AI 17555, AI 19657, RR 05443 and from the Rockefeller Foundation.     

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.     

The relationship of phosphodiesterase and cyclic AMP to the process of fluid secretion in the salivary glands of the ixodid tickAmblyomma americanum

Summary Phosphodiesterase (PDE) activity in the salivary glands of the female.Amblyomma americanum decreased as the tick progressed from a slow to a rapid phase of feeding, while the rate of fluid secretion increased, when glands were stimulated with cyclic AMP and theophylline Dopamine stimulated PDE activity and an inhibitory factor was found in glands obtained from rapidly engorging ticks which decreased PDE activity. These findings are discussed as they relate to the process of fluid secretion by salivary glands of feeding ixodid ticks.Journal article No. 3360 of Agricultural Experiment Station, Oklahoma State University, Stillwater, Oklahoma. This research was supported in part of NSF grant PCM-24140A02 from the National Science Foundation.     

Haemolymph ecdysteroids level following the injection of ecdysone or ecdysterone; its relation with tegument and midgut response inAeshna cyanea (Insecta,Odonata)

Summary The haemolymph ecdysteroid level after injection of ecdysone or ecdysterone inAeshna cyanea larvae has been determined by a radioimmunoassay method. The rate of excretion appears to be dependent on both the ecdysteroid injected and the time of injection. In case of ecdysone injection, the secretion of the epidermis cuticle and the differentiation of the imaginal midgut epithelium occur when the ecdysteroid level remains low for many days.     

Ecdysteroids: possible candidates for the hormone which triggers salivary gland degeneration in the ixodid tickAmblyomma hebraeum

Summary Following engorgement, female ixodid ticks secrete a tick salivary gland degeneration factor (TSGDF) into the hemolymph. Here we show that the arthropod ecdysteroid hormones, ecdysome and 20-hydroxyecdysone, induce degeneration of tick salivary glands maintained in organ culture. The effective dose range in vitro is 30–300 ng/ml, a range reported to be physiological for this species following repletion. In addition, infusion of 20-hydroxyecdysome in vivo induces salivary gland degeneration. We therefore propose that TSGDF may be an ecdysteroid.Acknowledgments. Some of the data reported here were presented to the annual meeting of the Canadian Society of Zoologists, 15–18 May 1983; Program of abstracts, page 53. Financial support of the Canadian National Sportsmen's Fund and NSERC Canada to W.R.K. is gratefully acknowledged.     

Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant

The development of non-infectious subunit vaccines greatly increases the safety of prophylactic immunization, but also reinforces the need for a new generation of immunostimulatory adjuvants. Because adverse effects are a paramount concern in prophylactic immunization, few new adjuvants have received approval for use anywhere in the developed world. The vaccine adjuvant monophosphoryl lipid A is a detoxified form of the endotoxin lipopolysaccharide, and is among the first of a new generation of Toll-like receptor agonists likely to be used as vaccine adjuvants on a mass scale in human populations. Much remains to be learned about this compound’s mechanism of action, but recent developments have made clear that it is unlikely to be simply a weak version of lipopolysaccharide. Instead, monophosphoryl lipid A’s structure seems to have fortuitously retained several functions needed for stimulation of adaptive immune responses, while shedding those associated with pro-inflammatory side effects. Received 25 April 2008; received after revision 05 June 2008; accepted 10 June 2008     

Variations des taux d'ecdystéroïdes au cours du développement deBombyx mori; rapport entre ces variations et les phases de croissance et de morphogenèse

Summary During the development ofBombyx mori (monovoltin race) ecdysteroid levels were determined in oocytes, eggs, and haemolymph of larvae, and in the haemolymph of pupae. In haemolymph, the only RIA reactive materials are ecdysone and ecdysterone. In oocytes and eggs, other ecdysteroids are also detected. During larval instars, the ecdysteroid levels are low whereas they are very high during morphogenetic periods. During embryonic diapause, the ecdysone titer decreases during the cessation of morphogenesis.     

Serotype-independent pneumococcal vaccines

Streptococcus pneumoniae remains an important cause of disease with high mortality and morbidity, especially in children and in the elderly. The widespread use of the polysaccharide conjugate vaccines in some countries has led to a significant decrease in invasive disease caused by vaccine serotypes, but an increase in disease caused by non-vaccine serotypes has impacted on the overall efficacy of these vaccines on pneumococcal disease. The obvious solution to overcome such shortcomings would be the development of new formulations that provide serotype-independent immunity. This review focuses on the most promising approaches, including protein antigens, whole cell pneumococcal vaccines, and recombinant bacteria expressing pneumococcal antigens. The protective capacity of these vaccine candidates against the different stages of pneumococcal infection, including colonization, mucosal disease, and invasive disease in animal models is reviewed. Some of the human trials that have already been performed or that are currently ongoing are presented. Finally, the feasibility and the possible shortcomings of these candidates in relation to an ideal vaccine against pneumococcal infections are discussed.     

Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata

A novel homologue of insect defensin designated lucifensin (Lucilia defensin) was purified from the extracts of various tissues (gut, salivary glands, fat body, haemolymph) of green bottle fly (Lucilia sericata) larvae and from their excretions/secretions. The primary sequence of this peptide of 40 residues and three intramolecular disulfide bridges was determined by ESI-QTOF mass spectrometry and Edman degradation and is very similar to that of sapecin and other dipteran defensins. We assume that lucifensin is the key antimicrobial component that protects the maggots when they are exposed to the highly infectious environment of a wound during the medicinal process known as maggot therapy. We also believe that lucifensin is that long-sought larger molecular weight antimicrobial factor of the Lucilia sericata excretions/secretions believed to be effective against pathogenic elements of the wound microbial flora.     

Effects and duration of resistance acquired by rabbits on feeding and egg laying in Ixodes ricinus L.

Rabbits gradually developed a resistance against Ixodes ricinus ticks as a result of sequential experimental infestations. The resistance was characterized by an increase duration of feeding, by ticks engorging to a smaller extent and by reduced egg production. Once established, the immunity persisted for at least 9 months. Changes in the titre of circulating anti-I. ricinus antibodies was measured by indirect immunofluorescence.     

Aggregation pheromones in 2 Australian hard ticks,Ixodes holocyclus and Aponomma concolor

Summary The presence of an aggregation pheromone has been demonstrated for the first time in indigenous Australian ticks. Filter paper discs exposed to either Australian paralysis ticks Ixodes holocyclus or echidna ticks Aponomma concolor showed inter-sex or intra-sex attraction for ticks of their own species. Nymphal exuviae of Ap. concolor were highly attractive to adult ticks. Discs were significantly attractive to I. holocyclus at distances up to 80 cm.Our thanks to Mr I. J. Lewis, Director, Cattle Tick Research Station, for initiating the study of possible pheromones in I. holocyclus, and for his continued encouragement throughout.