Profiling the Quality and Quantity of Naturally Induced Antibody Responses Against Pfs230 and Pfs48/45 Among Non-Febrile Children Living in Southern Ghana: A Longitudinal Study

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.

Potent transmission-blocking monoclonal antibodies from naturally exposed individuals target a conserved epitope on Plasmodium falciparum Pfs230

“… 20 , 54 Importantly, the humoral response to gametocyte TBV immunogens such as Pfs230 may be reinforced by prior and/or subsequent natural infection. 55 Humoral responses against Pfs230 are common in malaria endemic regions, 56 , 57 and we have recently shown that affinity-purified Pfs230-specific antibodies can indeed block transmission. 21 LMIV230-01 is the only other human-derived mAb reported to date with observed TRA 18 ( Figure 5 C) and is encoded by IGHV1-69 and IGKV1-5 , which were the most common germline genes identified from the memory B cells sequences obtained from the eight vaccinees in Coelho et al.…”

A potent and durable malaria transmission-blocking vaccine designed from a single-component 60-copy Pfs230D1 nanoparticle

“…Pfs230 is the most advanced TBV candidate and Pfs230D1-EPA 22 – 26 is currently in clinical trials (NCT02334462, NCT02942277, NCT03917654, NCT05135273). TBV candidates other than Pfs230 3 , 6 – 13 , 15 – 25 , 27 – 29 , 62 , 63 , 65 – 76 under clinical evaluation include Pfs25 3 , 62 – 64 and Pfs48/45 3 , 62 , 72 – 75 , and other antigens have been identified and are in development 35 , 77 .…”

Successive Site Translocating Inoculation Improved T Cell Responses Elicited by a DNA Vaccine Encoding SARS-CoV-2 S Protein

“…Avidity of Ag-specific Ab was determined by avidity ELISA as reported ( 15 – 17 ) with minor modifications. Briefly, plates were coated as the regular ELISA assay described above.…”