Immunity to blood stages of Plasmodium falciparum is dependent on a specific pattern of immunoglobulin subclass responses to multiple blood stage antigens

[[[ Background: ]]] In view of the lack of effectiveness of vaccines against Plasmodium falciparum malaria new approaches in the search for antigens and formulations for a vaccine are required. Immunoglobulin responses against several blood stage antigens were only partially associated with protection from symptoms in prospective immuno-epidemiological studies. [[[ Hypothesis: ]]] Immunity to blood stages of P. falciparum is dependent on a specific pattern of immunoglobulin subclass responses to multiple blood stage antigens. SUPPORTING EVIDENCE FOR THE HYPOTHESIS: This hypothesis results from previous studies showing that IgG1 and IgG3 responses against antigens like ring-infected erythrocyte surface antigens, merozoite surface proteins and variant surface antigens on schizonts were associated with clinical immunity against malaria. None of the specific responses against a single antigen was completely protective. [[[ Implications of the hypothesis: ]]] A confirmation of the hypothesis would support efforts to generate a P. falciparum vaccine containing a comprehensive set of blood stage antigens, which, using adjuvant technology, would lead to the appropriate immunoglobulin subclass response. MEANS TO TEST THE HYPOTHESIS: Detection of multiple immunorelevant P. falciparum blood stage antigens could be achieved by two-dimensional electrophoresis and blotting of the antigens onto nitrocellulose followed by exposure to the participant’s serum. Bound immunoglobulins are visualized by isotype specific peroxidase conjugated anti-human immunoglobulin and quantified by transmission densitometry. The resulting pattern of responses for each immunoglobulin isotype could be compared between clinically immune participants remaining asymptomatic with subsequent P. falciparum infections and people who develop malaria. Immunorelevant antigens are identifiable by mass spectrometry with the fully decoded P. falciparum genome.