Plasmodium berghei: Sporozoite challenge, protection, and hypersensitivity in mice

Alger, Nelda E.; Harant, Joyce

doi:10.1016/0014-4894(76)90091-6

Cited by 12 publications

(6 citation statements)

References 6 publications

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“…These authors conclude that the protective mechanism they observed was due to a host T-helper 1 response induced by sensitization against mosquito saliva and acting against pre-erythrocytic parasites that develop within the liver. In support of their own findings, these researchers (12) commented further that an older series of studies had used repeated vaccination with large amounts of mosquito salivary gland homogenate and demonstrated that this conferred partial protection to P. berghei infection in mice (1,2). Nevertheless, the only protection reported in these earlier studies was when both immunization and challenges were done intraperitoneally.…”

Section: Discussionmentioning

confidence: 81%

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

2010

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Malaria infection is initiated when a female Anopheles mosquito probing for blood injects saliva, together with sporozoites, into the skin of its mammalian host. Prior studies had suggested that saliva may enhance sporozoite infectivity. Using rodent malaria models (Plasmodium berghei and P. yoelii), we were unable to show that saliva had any detectable effect on sporozoite infectivity. This is encouraging for plans to immunize humans with washed, attenuated P. falciparum sporozoites because many individuals develop cutaneous, hypersensitivity reactions to mosquito saliva after repeated exposure. If washed sporozoites have no appreciable loss of infectivity, they likely do not have decreased immunogenicity; thus, vaccinees are unlikely to develop cutaneous reactions against mosquito saliva during attempted immunization with such sporozoites. Earlier studies also suggested that repeated prior exposure to mosquito saliva reduces infectivity of sporozoites injected by mosquitoes into sensitized hosts. However, our own studies show that prior exposure of mice to saliva had no detectable effect on numbers of sporozoites delivered by infected mosquitoes, the rate of disappearance of these sporozoites from the skin or infectivity of the sporozoites. Under natural conditions, sporozoites are delivered both to individuals who may exhibit cutaneous hypersensitivity to mosquito bite and to others who may have not yet developed such reactivity. It was tempting to hypothesize that differences in responsiveness to mosquito bite by different individuals might modulate the infectivity of sporozoites delivered into a milieu of changes induced by cutaneous hypersensitivity. Our results with rodent malaria models, however, were unable to support such a hypothesis.The malaria infection is initiated when a female Anopheles mosquito probing for a blood meal injects saliva, together with sporozoites into the skin of its mammalian host (18, 39). Mosquito saliva is known to enhance the ability of the mosquito to locate a blood source and to inhibit hemostasis by any of several mechanisms. These include injection of an anticoagulant factor (34), inhibition of platelet aggregation by salivary apyrase (29) or a salivary factor that inhibits collagen-induced platelet aggregation (43), inhibition of thrombin activity (14), and vasodilation of host blood vessels (30). Arthropod saliva has been shown to enhance the infectivity of several different pathogens introduced into hosts by arthropods; these include sandfly transmission of Leishmania, tick transmission of viruses and spirochetes, and mosquito transmission of viruses (for a review, see reference 36). Enhancement of Plasmodium sporozoite infectivity by mosquito saliva has also been reported (12, 36) based on a prior study (41), but we felt that this study needed to be reassessed.In addition to these studies on the direct effect of arthropod saliva on infectivity of pathogens injected by arthropods into immunologically naive hosts, studies have also been done on the role of prior exposure...

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Section: Discussionmentioning

confidence: 81%

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

2010

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“…It is possible that residual salivary components remaining from the isolation of sporozoites can partially explain the protection observed in the studies involving radiation-attenuated sporozoites. One original study investigating irradiated sporozoites as vaccine components used repeated vaccination with large amounts of mosquito salivary gland homogenate (SGH; 70 glands) as a control and demonstrated that this procedure confers partial protection to Plasmodium berghei infection in mice (1,2). More recently, it has been demonstrated that Plasmodium gallinaceum parasitemia levels are increased in the presence of Aedes fluviatilis saliva in a chicken malaria model, a response that was reversed with prior exposure to mosquito saliva (43).…”

Section: Resultsmentioning

confidence: 99%

Uninfected Mosquito Bites Confer Protection against Infection with Malaria Parasites

et al. 2007

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Despite decades of research and multiple initiatives, malaria continues to be one of the world's most debilitating infectious diseases. New insights for malaria control and vaccine development will be essential to thwart the staggering worldwide impact of this disease ( . Using a murine model of malaria infection, we show here that exposure to bites from uninfected mosquitoes prior to Plasmodium yoelii infection influences the local and systemic immune responses and limits parasite development within the host. In hosts preexposed to bites from uninfected mosquitoes, reduced parasite burdens in the livers were detected early, and during the blood-stage of the life cycle, these burdens remained lower than those in hosts that received mosquito bites only at the time of infection. Repeated exposure to bites from uninfected mosquitoes skewed the immune response towards a T-helper 1 (Th1) phenotype as indicated by increased levels of interleukin-12, gamma interferon, and inducible nitric oxide synthase. These data suggest that the addition of mosquito salivary components to antimalaria vaccines may be a viable strategy for creating a Th1-biased environment known to be effective against malaria infection. Furthermore, this strategy may be important for the development of vaccines to combat other mosquitotransmitted pathogens.

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“…Indeed, earlier work by others indicated that a vectorbased vaccine might be effective. For example, vector saliva can modify the course of infection with bacteria (29,30), viruses (8,10,31), and parasites (32,33). Finally, recent work by Kamhawi et al (34) showed that the bite of uninfected sandflies (this work used Phlebotomus papatasi sandflies; MAX is a protein found in L. longipalpis salivary glands) conferred resistance to a subsequent infection with L. major.…”

Section: Figurementioning

confidence: 88%

Sandfly Maxadilan Exacerbates Infection with Leishmania major and Vaccinating Against It Protects Against L. major Infection

Morris

Shoemaker

David

et al. 2001

The Journal of Immunology

203

191

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Bloodfeeding arthropods transmit many of the world’s most serious infectious diseases. Leishmania are transmitted to their mammalian hosts when an infected sandfly probes in the skin for a bloodmeal and injects the parasite mixed with its saliva. Arthropod saliva contains molecules that affect blood flow and modulate the immune response of the host. Indeed, sandfly saliva markedly enhances the infectivity of L. major for its host. If the salivary molecule(s) responsible for this phenomenon was identified, it might be possible to vaccinate the host against this molecule and thereby protect the host against infection with Leishmania. Such an approach represents a novel means of controlling arthropod-borne disease transmission. Here, we report that a single molecule, maxadilan, in sandfly saliva can exacerbate infection with L. major to the same degree as whole saliva, and that vaccinating against maxadilan protects mice against infection with L. major.

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Plasmodium berghei: Sporozoite challenge, protection, and hypersensitivity in mice

Cited by 12 publications

References 6 publications

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

Neither Mosquito Saliva nor Immunity to Saliva Has a Detectable Effect on the Infectivity ofPlasmodiumSporozoites Injected into Mice

Uninfected Mosquito Bites Confer Protection against Infection with Malaria Parasites

Sandfly Maxadilan Exacerbates Infection with Leishmania major and Vaccinating Against It Protects Against L. major Infection

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