TY - JOUR
T1 - Effect of hookworm infection and anthelmintic treatment on naturally acquired antibody responses against the GMZ2 malaria vaccine candidate and constituent antigens
AU - Amoani, Benjamin
AU - Gyan, Ben
AU - Sakyi, Samuel Asamoah
AU - Abu, Emmanuel Kwasi
AU - Nuvor, Samuel Victor
AU - Barnes, Precious
AU - Sarkodie-Addo, Tracy
AU - Ahenkorah, Benjamin
AU - Sewor, Christian
AU - Dwomoh, Duah
AU - Theisen, Michael
AU - Cappello, Michael
AU - Wilson, Michael D
AU - Adu, Bright
PY - 2021/4/8
Y1 - 2021/4/8
N2 - BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
AB - BACKGROUND: Malaria and helminths diseases are co-endemic in most parts of sub-Saharan Africa. Immune responses from each of these pathogens interact, and these interactions may have implications on vaccines. The GMZ2 malaria vaccine candidate is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP R0). GMZ2 has recently showed modest efficacy in a phase IIb multicenter trial. Here, we assessed the effect of hookworm (Necator americanus) infection and anthelmintic treatment on naturally acquired antibody responses against GMZ2 and constituent antigens.METHODS: This longitudinal cross-sectional study was conducted in the Kintampo North Municipality of Ghana. Blood and stool samples were taken from 158 individuals (4-88 years old) infected with either P. falciparum alone (n = 59) or both hookworm and P. falciparum (n = 63) and uninfected endemic controls (n = 36). Stool hookworm infection was detected by the Kato-Katz method and PCR. Malaria parasitaemia was detected by RDT, light microscopy and P. falciparum-specific 18S rRNA gene PCR. Serum samples were obtained prior to hookworm treatment with a single dose of albendazole (400 mg) and 3 weeks (21 days) after treatment. Levels of IgG1, IgG3 and IgM against GMZ2, MSP3 and GLURP R0 were measured by ELISA and compared among the groups, before and after treatment.RESULTS: Participants with P. falciparum and hookworm co-infection had significantly higher IgG3 levels to GMZ2 than those with only P. falciparum infection and negative control (p < 0.05) at baseline. Treatment with albendazole led to a significant reduction in IgG3 levels against both GMZ2 and GLURP R0. Similarly, IgM and IgG1 levels against MSP3 also decreased following deworming treatment.CONCLUSION: Individuals with co-infection had higher antibody responses to GMZ2 antigen. Treatment of hookworm/malaria co-infection resulted in a reduction in antibody responses against GMZ2 and constituent antigens after albendazole treatment. Thus, hookworm infection and treatment could have a potential implication on malaria vaccine efficacy.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Albendazole/therapeutic use
KW - Anthelmintics/therapeutic use
KW - Antibodies, Protozoan/blood
KW - Antigens, Protozoan/immunology
KW - Case-Control Studies
KW - Child
KW - Child, Preschool
KW - Cross-Sectional Studies
KW - Female
KW - Hookworm Infections/drug therapy
KW - Humans
KW - Immunoglobulin G/blood
KW - Longitudinal Studies
KW - Malaria Vaccines/genetics
KW - Malaria, Falciparum/immunology
KW - Male
KW - Middle Aged
KW - Parasitemia/parasitology
KW - Protozoan Proteins/immunology
KW - Young Adult
UR - http://www.scopus.com/inward/record.url?scp=85104050083&partnerID=8YFLogxK
U2 - 10.1186/s12879-021-06027-5
DO - 10.1186/s12879-021-06027-5
M3 - Journal article
C2 - 33832450
SN - 1471-2334
VL - 21
SP - 332
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 332
ER -