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Abstract
A clear understanding of the properties of naturally induced antibody responses against transmission-blocking vaccine candidates can accelerate the understanding of the development of transmission-blocking immunity. This study characterized the naturally induced IgG responses against two leading transmission-blocking vaccine antigens, Pfs230 and Pfs48/45, in non-febrile children living in Simiw, Ghana. Consecutive sampling was used to recruit 84 non-febrile children aged from 6 to 12 years old into the 6-month (November 2017 until May 2018) longitudinal study. Venous blood (1 ml) was collected once every 2 months and used to determine hemoglobin levels, P. falciparum prevalence using microscopy and polymerase chain reaction, and the levels and relative avidity of IgG responses against Pfs230 and Pfs48/45 using indirect ELISA. IgG levels against Pfs230 and Pfs48/45 decreased from the start (November) to the middle (January) and end (March) of the dry season respectively, then they began to increase. Participants, especially older children (10–12 years old) with active infections generally had lower antibody levels against both antigens. The relative avidities of IgG against both antigens followed the trend of IgG levels until the middle of the dry season, after which the relative avidities of both antigens correlated inversely with the antibody levels. In conclusion, although IgG antibody levels against both Pfs48/45 and Pfs230 began to increase by the early rainy season, they were inversely correlated to their respective relative avidities.
Highlights
The cycle of malaria transmission can be broken by the development of an immune response that arrests the progress of the infectious stages of the parasite, including gametocytes
Enhanced knowledge of the properties of naturally induced antibody responses against these antigens can help accelerate the understanding of malaria transmission-blocking vaccine (MTBV) candidate development
Parasite prevalence estimated by polymerase chain reaction was highest (74.4%) in May and lowest (27.3%) in January
Summary
The cycle of malaria transmission can be broken by the development of an immune response that arrests the progress of the infectious stages of the parasite, including gametocytes. The Pfs230 is a 3,135 amino acid (aa) protein containing 14 s48/45 6-Cys domains (Williamson & Kaslow, 1993) and Pfs48/45 is a 448 aa protein containing 3 s48/ 45 6-Cys domain (Outchkourov et al, 2008). Antibodies against both Pfs230 and Pfs48/45 antigens possess transmission-reducing activities and are able to prevent the completion of the sporogonic life cycle of the malaria parasite within the mosquito vector (Kumar et al, 1995; Bousema et al, 2006). Children have been identified to efficiently harbor gametocytes (Lamptey et al, 2018) and make them a relevant group to study the quality (avidity) and quantity (level) of naturally induced IgG responses against gametocyte antigens
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