A Framework for Controlled Human Infection Model (CHIM) Studies in Malawi: Report of a Wellcome Trust Workshop on CHIM in Low Income Countries Held in Blantyre, Malawi

Overview

Journal Wellcome Open Res

Specialty Biomedical Engineering

Date 2017 Oct 12

PMID 29018841

Citations 42

Authors

Stephen B Gordon

Jamie Rylance

Amy Luck

Kondwani Jambo

Daniela M Ferreira

Lucinda Manda-Taylor

Philip Bejon

Bagrey Ngwira

Katherine Littler

Zoe Seager

Malick Gibani

Markus Gmeiner

Meta Roestenberg

Yohannie Mlombe

Affiliations

Soon will be listed here.

Abstract

Controlled human infection model (CHIM) studies have pivotal importance in vaccine development, being useful for proof of concept, pathogenesis, down-selection and immunogenicity studies. To date, however, they have seldom been carried out in low and middle income countries (LMIC), which is where the greatest burden of vaccine preventable illness is found. This workshop discussed the benefits and barriers to CHIM studies in Malawi. Benefits include improved vaccine effectiveness and host country capacity development in clinical, laboratory and governance domains. Barriers include acceptability, safety and regulatory issues. The report suggests a framework by which ethical, laboratory, scientific and governance issues may be addressed by investigators considering or planning CHIM in LMIC.

Citing Articles

Immune correlates of protection as a game changer in tuberculosis vaccine development.

Wang J, Fan X, Hu Z NPJ Vaccines. 2024; 9(1):208.

PMID: 39478007 PMC: 11526030. DOI: 10.1038/s41541-024-01004-w.

Public engagement for the conduct of a controlled human infection study testing vaccines against Necator americanus (hookworm) in areas of active hookworm transmission in Brazil.

Barra Ribeiro L, Gazzinelli A, Santiago H, Fiuza J, Lobato L, Correa de Oliveira R PLoS One. 2024; 19(6):e0299022.

PMID: 38829836 PMC: 11146735. DOI: 10.1371/journal.pone.0299022.

Reverse development of vaccines against antimicrobial-resistant pathogens.

Bagnoli F, Galgani I, Vadivelu V, Phogat S NPJ Vaccines. 2024; 9(1):71.

PMID: 38570502 PMC: 10991305. DOI: 10.1038/s41541-024-00858-4.

Neglected tropical disease vaccines: hookworm, leishmaniasis, and schistosomiasis.

Hotez P, Bottazzi M, Kaye P, Lee B, Puchner K Vaccine. 2024; 41 Suppl 2:S176-S179.

PMID: 38407985 PMC: 10713477. DOI: 10.1016/j.vaccine.2023.04.025.

Experimental pneumococcal carriage in people living with HIV in Malawi: the first controlled human infection model in a key at-risk population.

Doherty K, Dula D, Chirwa A, Nsomba E, Nkhoma V, Toto N Wellcome Open Res. 2024; 9:2.

PMID: 38362541 PMC: 10864820. DOI: 10.12688/wellcomeopenres.19949.1.

References

Miller F, Grady C . The ethical challenge of infection-inducing challenge experiments. Clin Infect Dis. 2001; 33(7):1028-33. DOI: 10.1086/322664. View

Balasingam S, Horby P, Wilder-Smith A . The potential for a controlled human infection platform in Singapore. Singapore Med J. 2014; 55(9):456-61. PMC: 4293939. DOI: 10.11622/smedj.2014114. View

Shirley D, McArthur M . The utility of human challenge studies in vaccine development: lessons learned from cholera. Vaccine (Auckl). 2014; 2011(1):3-13. PMC: 3904492. DOI: 10.2147/VDT.S23634. View

Kester K, Cummings J, Ofori-Anyinam O, Ockenhouse C, Krzych U, Moris P . Randomized, double-blind, phase 2a trial of falciparum malaria vaccines RTS,S/AS01B and RTS,S/AS02A in malaria-naive adults: safety, efficacy, and immunologic associates of protection. J Infect Dis. 2009; 200(3):337-46. DOI: 10.1086/600120. View

Shekalaghe S, Rutaihwa M, Billingsley P, Chemba M, Daubenberger C, James E . Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2014; 91(3):471-480. PMC: 4155546. DOI: 10.4269/ajtmh.14-0119. View

Gilman R, Hornick R, Woodard W, DuPont H, Snyder M, Levine M . Evaluation of a UDP-glucose-4-epimeraseless mutant of Salmonella typhi as a liver oral vaccine. J Infect Dis. 1977; 136(6):717-23. DOI: 10.1093/infdis/136.6.717. View

Allison A . Protection afforded by sickle-cell trait against subtertian malareal infection. Br Med J. 1954; 1(4857):290-4. PMC: 2093356. DOI: 10.1136/bmj.1.4857.290. View

Gibani M, Jin C, Darton T, Pollard A . Control of Invasive Salmonella Disease in Africa: Is There a Role for Human Challenge Models?. Clin Infect Dis. 2015; 61 Suppl 4:S266-71. PMC: 4596929. DOI: 10.1093/cid/civ673. View

Darton T, Blohmke C, Moorthy V, Altmann D, Hayden F, Clutterbuck E . Design, recruitment, and microbiological considerations in human challenge studies. Lancet Infect Dis. 2015; 15(7):840-51. DOI: 10.1016/S1473-3099(15)00068-7. View

10.

Roestenberg M, de Vlas S, Nieman A, Sauerwein R, Hermsen C . Efficacy of preerythrocytic and blood-stage malaria vaccines can be assessed in small sporozoite challenge trials in human volunteers. J Infect Dis. 2012; 206(3):319-23. DOI: 10.1093/infdis/jis355. View

11.

Bodhidatta L, Pitisuttithum P, Chamnanchanant S, Chang K, Islam D, Bussaratid V . Establishment of a Shigella sonnei human challenge model in Thailand. Vaccine. 2012; 30(49):7040-5. PMC: 3732056. DOI: 10.1016/j.vaccine.2012.09.061. View

12.

Hodgson S, Juma E, Salim A, Magiri C, Njenga D, Molyneux S . Lessons learnt from the first controlled human malaria infection study conducted in Nairobi, Kenya. Malar J. 2015; 14:182. PMC: 4416324. DOI: 10.1186/s12936-015-0671-x. View

13.

Chattopadhyay R, Pratt D . Role of controlled human malaria infection (CHMI) in malaria vaccine development: A U.S. food & drug administration (FDA) perspective. Vaccine. 2017; 35(21):2767-2769. DOI: 10.1016/j.vaccine.2017.03.072. View