AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5.
BACKGROUND
Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated.


METHODS
Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline.


RESULTS
AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses.


CONCLUSIONS
Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.
Bracho
Gustavo
G
Department of Immunology, Finlay Institute, Havana City, Cuba. gbracho@finlay.edu.cu
Zayas
Caridad
C
Wang
Lina
L
Coppel
Ross
R
Pérez
Oliver
O
Petrovsky
Nikolai
N
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D015848:Interleukin-5; D017780:Malaria Vaccines; D008565:Membrane Proteins; D022401:Meningococcal Vaccines; D015800:Protozoan Proteins; C118839:merozoite surface protein 4, Plasmodium; C114957:merozoite surface protein 5; D007371:Interferon-gamma; D005620:Freund's Adjuvant