Controlled human malaria infection (CHMI) outcomes in Kenyan adults is associated with prior history of malaria exposure and anti-schizont antibody response

Melissa C Kapulu, Domtila Kimani, Patricia Njuguna, Mainga Hamaluba, Edward Otieno, Rinter Kimathi, James Tuju, B Kim Lee Sim, CHMI-SIKA Study Team, Abdirahman I Abdi, Yonas Abebe, Philip Bejon, Peter F Billingsley, Peter C Bull, Zaydah de Laurent, Stephen L Hoffman, Eric R James, Silvia Kariuki, Sam Kinyanjui, Cheryl Kivisi, Johnstone Makale, Kevin Marsh, Khadija Said Mohammed, Moses Mosobo, Janet Musembi, Jennifer Musyoki, Michelle Muthui, Jedidah Mwacharo, Kennedy Mwai, Joyce M Ngoi, Omar Ngoto, Irene Nkumama, Francis Ndungu, Dennis Odera, Bernhards Ogutu, Fredrick Olewe, Donwilliams Omuoyo, John Ong'echa, Faith Osier, Thomas L Richie, Jimmy Shangala, Juliana Wambua, Thomas N Williams, Melissa C Kapulu, Domtila Kimani, Patricia Njuguna, Mainga Hamaluba, Edward Otieno, Rinter Kimathi, James Tuju, B Kim Lee Sim, CHMI-SIKA Study Team, Abdirahman I Abdi, Yonas Abebe, Philip Bejon, Peter F Billingsley, Peter C Bull, Zaydah de Laurent, Stephen L Hoffman, Eric R James, Silvia Kariuki, Sam Kinyanjui, Cheryl Kivisi, Johnstone Makale, Kevin Marsh, Khadija Said Mohammed, Moses Mosobo, Janet Musembi, Jennifer Musyoki, Michelle Muthui, Jedidah Mwacharo, Kennedy Mwai, Joyce M Ngoi, Omar Ngoto, Irene Nkumama, Francis Ndungu, Dennis Odera, Bernhards Ogutu, Fredrick Olewe, Donwilliams Omuoyo, John Ong'echa, Faith Osier, Thomas L Richie, Jimmy Shangala, Juliana Wambua, Thomas N Williams

Abstract

Background: Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure.

Methods: We analysed data from 142 Kenyan adults from three locations representing distinct areas of malaria endemicity (Ahero, Kilifi North and Kilifi South) enrolled in a CHMI study with Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify the in vivo outcomes that most closely reflected naturally acquired immunity, parameters based on qPCR measurements were compared with anti-schizont antibody levels and residence as proxy markers of naturally acquired immunity.

Results: Time to endpoint correlated more closely with anti-schizont antibodies and location of residence than other parasite parameters such as growth rate or mean parasite density. Compared to observational field-based studies in children where 0.8% of the variability in malaria outcome was observed to be explained by anti-schizont antibodies, in the CHMI model the dichotomized anti-schizont antibodies explained 17% of the variability.

Conclusions: The CHMI model is highly effective in studying markers of naturally acquired immunity to malaria. Trial registration Clinicaltrials.gov number NCT02739763. Registered 15 April 2016.

Keywords: Anti-schizont antibody response; Controlled human malaria infection; Malaria exposure; Plasmodium falciparum.

Conflict of interest statement

B. K. L. S. is a salaried, full-time employee of Sanaria Inc., the manufacturer of Sanaria PfSPZ Challenge. Thus, all authors associated with Sanaria Inc. have potential conflicts of interest. All other authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Time to treatment survival analysis. Kaplan–Meier curves comparing time to treatment with location of residence (left panel) and anti-schizont antibody response (right panel). Shown are survival curves for location of residence is low transmission (blue) vs. high transmission (red). For anti-schizont antibody responses shown is low antibodies (blue) vs. high antibodies (red)
Fig. 2
Fig. 2
Survival analysis of CHMI vs. field-based observational study. Kaplan–Meier curves comparing of the CHMI cohort (left panel) and field-based cohort (right panel) in relation to requirement for treatment and anti-schizont antibody responses. Antibody responses are shown as low (red) vs. high (blue)

References

    1. Kamau A, Mogeni P, Okiro EA, Snow RW, Bejon P. A systematic review of changing malaria disease burden in sub-Saharan Africa since 2000: comparing model predictions and empirical observations. BMC Med. 2020;18:1–11. doi: 10.1186/s12916-020-01559-0.
    1. Agnandji ST, Lell B, Soulanoudjingar SS, Fernandes JF, Abossolo BP, Conzelmann C, et al. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med. 2011;365:1863–1875. doi: 10.1056/NEJMoa1102287.
    1. Datoo MS, Natama MH, Somé A, Traoré O, Rouamba T, Bellamy D, et al. Efficacy of a low-dose candidate malaria vaccine, R21 in adjuvant Matrix-M, with seasonal administration to children in Burkina Faso: a randomised controlled trial. Lancet. 2021;397:1809–1818. doi: 10.1016/S0140-6736(21)00943-0.
    1. Duffy PE, Patrick Gorres J. Malaria vaccines since 2000: progress, priorities, products. npj Vaccines. 2020;5:1–9. doi: 10.1038/s41541-020-0196-3.
    1. Ogutu BR, Apollo OJ, McKinney D, Okoth W, Siangla J, Dubovsky F, et al. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS ONE. 2009;4:e4708. doi: 10.1371/journal.pone.0004708.
    1. Thera MA, Doumbo OK, Coulibaly D, Laurens MB, Ouattara A, Kone AK, et al. A field trial to assess a blood-stage malaria vaccine. N Engl J Med. 2011;365:1004–1013. doi: 10.1056/NEJMoa1008115.
    1. Fowkes FJI, Richards JS, Simpson JA, Beeson JG. The relationship between anti-merozoite antibodies and incidence of Plasmodium falciparum malaria: a systematic review and meta-analysis. PLoS Med. 2010;7:e1000218. doi: 10.1371/journal.pmed.1000218.
    1. Ndungu FM, Marsh K, Fegan G, Wambua J, Nyangweso G, Ogada E, et al. Identifying children with excess malaria episodes after adjusting for variation in exposure: identification from a longitudinal study using statistical count models. BMC Med. 2015;13:1–8. doi: 10.1186/s12916-015-0422-4.
    1. Bejon P, Warimwe G, Mackintosh CL, Mackinnon MJ, Kinyanjui SM, Musyoki JN, et al. Analysis of immunity to febrile malaria in children that distinguishes immunity from lack of exposure. Infect Immun. 2009;77:1917–1923. doi: 10.1128/IAI.01358-08.
    1. Beeson JG, Osier FH, Engwerda CR. Recent insights into humoral and cellular immune responses against malaria. Trends Parasitol. 2008;24:578–548. doi: 10.1016/j.pt.2008.08.008.
    1. Osier FH, Mackinnon MJ, Crosnier C, Fegan G, Kamuyu G, Wanaguru M, et al. Malaria: new antigens for a multicomponent blood-stage malaria vaccine. Sci Transl Med. 2014;6:247ra102. doi: 10.1126/scitranslmed.3008705.
    1. Drakeley CJ, Corran PH, Coleman PG, Tongren JE, McDonald SLR, Carneiro I, et al. Estimating medium- and long-term trends in malaria transmission by using serological markers of malaria exposure. Proc Natl Acad Sci USA. 2005;102:5108–5113. doi: 10.1073/pnas.0408725102.
    1. Manske M, Miotto O, Campino S, Auburn S, Almagro-Garcia J, Maslen G, et al. Analysis of Plasmodium falciparum diversity in natural infections by deep sequencing. Nature. 2012;487:375–379. doi: 10.1038/nature11174.
    1. Kamau A, Mtanje G, Mataza C, Mwambingu G, Mturi N, Mohammed S, et al. Malaria infection, disease and mortality among children and adults on the coast of Kenya. Malar J. 2020;19:210. doi: 10.1186/s12936-020-03286-6.
    1. Kapulu MC, Njuguna P, Hamaluba M, Kimani D, Ngoi JM, Musembi J, et al. Safety and PCR monitoring in 161 semi-immune Kenyan adults following controlled human malaria infection. JCI Insight. 2021 doi: 10.1172/jci.insight.146443.
    1. Achan J, Reuling I, Yap XZ, Dabira E, Ahmad A, Cox M, et al. Serologic markers of previous malaria exposure and functional antibodies inhibiting parasite growth are associated with parasite kinetics following a Plasmodium falciparum controlled human infection. Clin Infect Dis. 2019 doi: 10.1093/cid/ciz740.
    1. Lell B, Mordmuller B, Dejon Agobe JC, Honkpehedji J, Zinsou J, Mengue JB, et al. Impact of sickle cell trait and naturally acquired immunity on uncomplicated malaria after controlled human malaria infection in adults in Gabon. Am J Trop Med Hyg. 2017 doi: 10.4269/ajtmh.17-0343.
    1. Kapulu MCMC, Njuguna P, Hamaluba MMM, Abdi AIAI, Abebe Y, Audi A, et al. Controlled human malaria infection in semi-immune Kenyan adults (Chmi-sika): a study protocol to investigate in vivo plasmodium falciparum malaria parasite growth in the context of pre-existing immunity [version 2; peer review: 2 approved] Wellcome Open Res. 2019;3:155. doi: 10.12688/wellcomeopenres.14909.2.
    1. Gómez-Pérez GP, Legarda A, Muñoz J, Sim BKL, Ballester MR, Dobaño C, et al. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates. Malar J. 2015;14:306. doi: 10.1186/s12936-015-0817-x.
    1. Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, et al. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015;14:117. doi: 10.1186/s12936-015-0628-0.
    1. Moser KA, Drábek EF, Dwivedi A, Stucke EM, Crabtree J, Dara A, et al. Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential. Genome Med. 2020;12:1–17. doi: 10.1186/s13073-019-0708-9.
    1. Hodgson SH, Juma E, Salim A, Magiri C, Kimani D, Njenga D, et al. Evaluating controlled human malaria infection in Kenyan adults with varying degrees of prior exposure to Plasmodium falciparum using sporozoites administered by intramuscular injection. Front Microbiol. 2014;5:686. doi: 10.3389/fmicb.2014.00686.
    1. Osier FH, Fegan G, Polley SD, Murungi L, Verra F, Tetteh KK, et al. Breadth and magnitude of antibody responses to multiple Plasmodium falciparum merozoite antigens are associated with protection from clinical malaria. Infect Immun. 2008;76:2240–2248. doi: 10.1128/IAI.01585-07.
    1. Snow RW, Sartorius B, Kyalo D, Maina J, Amratia P, Mundia CW, et al. The prevalence of Plasmodium falciparum in sub-Saharan Africa since 1900. Nature. 2017;550:515–518. doi: 10.1038/nature24059.
    1. Ogwang C, Afolabi M, Kimani D, Jagne YJ, Sheehy SH, Bliss CM, et al. Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults. PLoS ONE. 2013;8:e57726. doi: 10.1371/journal.pone.0057726.
    1. Cunningham JA, Thomson RM, Murphy SC, De La Paz Ade M, Ding XC, Incardona S, et al. WHO malaria nucleic acid amplification test external quality assessment scheme: results of distribution programmes one to three. Malar J. 2020;19:1–12. doi: 10.1186/s12936-020-03200-0.
    1. Church LWP, Le TP, Bryan JP, Gordon DM, Edelman R, Fries L, et al. Clinical manifestations of Plasmodium falciparum malaria experimentally induced by mosquito challenge. J Infect Dis. 1997;175:915–920. doi: 10.1086/513990.
    1. Epstein JE, Rao S, Williams F, Freilich D, Luke T, Sedegah M, et al. Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. J Infect Dis. 2007;196:145–154. doi: 10.1086/518510.
    1. Minassian AM, Silk SE, Barrett JR, Nielsen CM, Miura K, Diouf A, et al. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination. Med. 2021;2:701–719.e19. doi: 10.1016/j.medj.2021.03.014.
    1. Wockner LF, Hoffmann I, Webb L, Mordmüller B, Murphy SC, Kublin JG, et al. Growth rate of Plasmodium falciparum: analysis of parasite growth data from malaria volunteer infection studies. J Infect Dis. 2020;221:963–972. doi: 10.1093/infdis/jiz557.
    1. Shekalaghe S, Rutaihwa M, Billingsley PF, Chemba M, Daubenberger CA, James ER, et al. Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2014;91:471–480. doi: 10.4269/ajtmh.14-0119.
    1. Hodgson SH, Llewellyn D, Silk SE, Milne KH, Elias SC, Miura K, et al. Changes in serological immunology measures in UK and Kenyan adults post-controlled human malaria infection. Front Microbiol. 2016;7:1604. doi: 10.3389/fmicb.2016.01604.
    1. Murungi LM, Sondén K, Llewellyn D, Rono J, Guleid F, Williams AR, et al. Targets and mechanisms associated with protection from severe Plasmodium falciparum malaria in Kenyan children. Infect Immun. 2016;84:950–963. doi: 10.1128/IAI.01120-15.
    1. Joos C, Marrama L, Polson HEJ, Corre S, Diatta A-M, Diouf B, et al. Clinical protection from Falciparum malaria correlates with neutrophil respiratory bursts induced by merozoites opsonized with human serum antibodies. PLoS ONE. 2010;5:e9871. doi: 10.1371/journal.pone.0009871.
    1. Osier FH, Feng G, Boyle MJ, Langer C, Zhou J, Richards JS, et al. Opsonic phagocytosis of Plasmodium falciparum merozoites: mechanism in human immunity and a correlate of protection against malaria. BMC Med. 2014;12:108. doi: 10.1186/1741-7015-12-108.
    1. Kamuyu G, Tuju J, Kimathi R, Mwai K, Mburu J, Kibinge N, et al. KILchip v1.0: a novel Plasmodium falciparum merozoite protein microarray to facilitate malaria vaccine candidate prioritization. Front Immunol. 2018;9:2866. doi: 10.3389/fimmu.2018.02866.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir