Abstract

The midgut of the malaria - transmitting mosquito, Anopheles gambiae, can be targeted by vaccine-induced host immune factors that kill the mosquito after it ingests immunized host blood. The An. gambiae mucin 1 protein (AgMuc1) is expressed on the mosquito midgut where it likely functions in protecting the midgut epithelium from its own secreted digestive enzymes, toxic substances and pathogenic microbes taken in with the blood meal. Immunization of mice with plasmid containing the AgMuc1 gene has been shown to induce mosquitocidal immune responses. In this paper, we co-immunized mice with AgMuc1 cDNA and plasmid containing Murine granulocyte-macrophage stimulating factor (GM-CSF) or Interleukin 12 (IL-12) cytokine cDNA in order to further potentiate the mosquitocidal immune response and better define the nature of this mosquitocidal immunity. While co-immunization with GM-CSF cDNA failed to increase anti-mosquito immunity (Chisq = 3.3 on 1 degree of freedom, p = 0.068), a significantly enhanced mosquitocidal effect was observed from mice co-immunized with AgMuc1 and IL-12 cDNA (Chisq = 39.1 on I degree of freedom, p = 4.06e-10). Furthermore, the cumulative survival of the blood fed mosquitoes surviving to day 7 in the AgMuc1/IL-12 co-immunized group highly correlated negatively with the anti-mucin IgG1 antibody subtype levels (Pearson correlation coefficient r = -0.782) suggesting that the mosquitocidal immunity induced by AgMuc1 cDNA immunization could be IgG1 antibody subtype mediated.

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