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

Abstract

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...

Members of the Salivary Gland Surface Protein (SGS) Family Are Major Immunogenic Components of Mosquito Saliva

“…Accordingly, vaccines that help incite the host antibody response against salivary immunomodulatory factors have been shown to lower the transmission rates of Leishmania parasites and have been proposed for use against other arthropodvectored diseases (4,11). Although mosquito saliva has conclusively been shown to enhance the transmission of several viruses (10), its role in the transmission of malaria parasites remains a point of contention (12)(13)(14). Thus, the identification of novel immunomodulatory components of mosquito saliva may aid in the development of disease control strategies.…”

Impact of Mosquito Bites on Asexual Parasite Density and Gametocyte Prevalence in Asymptomatic Chronic Plasmodium falciparum Infections and Correlation with IgE and IgG Titers

“…In conclusion, this work contributes to the ongoing debate concerning the targeting of mosquito saliva components as a strategy for malaria control (16,25). In contrast to the focus on the initial stages of infection in naïve hosts, our work suggests that there may be longer-term effects of mosquito saliva that promote parasite persistence in chronic infections.…”

“…There is conflicting evidence concerning a role for mosquito saliva in facilitating the initiation of an infection by Plasmodium sporozoites (25,49). Here we provide evidence that mosquito saliva has a demonstrable impact on the parasite during the chronic asymptomatic stage of infection.…”

“…While prior exposure to arthropod saliva can exacerbate infection, immunity against saliva antigens has also been shown to protect against a severe outcome of disease for both Leishmania (22) and Plasmodium (16) infections. Interestingly, immunity to saliva does not have an impact on sporozoite infectivity (25).…”

Immunological consequences of arthropod vector‐derived salivary factors

“…Mounting evidence indicates that these pathogens have evolved to take advantage of specific salivary proteins and sugars to facilitate the establishment of an infection. However, no clear picture of the role of arthropod saliva during infection emerges in the literature; some reports indicate that salivary factors help the pathogen [21], interfere with infection in others [22], or have no apparent effect in other models [23]. Furthermore, the timing of the exposure to the saliva appears to be critical: while sand fly saliva present during infection with Leishmania exacerbates infection, pre-exposure to the same saliva components induces protective immunity [24,25].…”