The development of protective
vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two
antigens from the blood-stage merozoite of the Plasmodium falciparum human
malaria parasite--MSP1 and AMA1. These
antigens were delivered to healthy
malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human
malaria infection (
CHMI) with P. falciparum to assess
vaccine efficacy, whereby all but one volunteer developed low-density blood-stage
parasitemia. Here we assess serum antibody responses against both the
MSP1 and AMA1
antigens following i) ChAd63-MVA immunization, ii) immunization and
CHMI, and iii) primary
malaria exposure in the context of
CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural
malaria exposure. Serum antibody responses against
MSP1 and AMA1 were characterized in terms of i) total
IgG responses before and after
CHMI, ii) responses to allelic variants of
MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv)
IgG avidity, and v) isotype responses (
IgG1-4,
IgA and
IgM). These data provide the first in-depth assessment of the quality of adenovirus-
MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these
malaria antigens depending on the means of their induction and/or exposure of the host to the
malaria parasite. Given the continued clinical development of viral vectored
vaccines for
malaria and a range of other diseases targets, these data should help to guide further immuno-monitoring studies of
vaccine-induced human antibody responses.