Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming.
We have previously shown that a DNA-prime followed by an adenovirus-5 boost vaccine containing CSP and AMA1 (DNA/Ad) successfully protected 4 of 15 subjects to controlled human malaria infection (CHMI). However, the adenovirus-5 vaccine alone (AdCA) failed to induce protection despite eliciting cellular responses that were often higher than those induced by DNA/Ad. Here we determined the effect of CHMI on pre-CHMI cellular and antibody responses against CSP and AMA1 expressed as fold-changes in activities. Generally, in the DNA/Ad trial, CHMI caused pre-CHMI ELISpot IFN-γ and CD8+ T cell IFN-γ responses of the protected subjects to fall but among non-protected subjects, CHMI caused rises of pre-CHMI ELISpot IFN-γ but falls of CD8+ T cell IFN-γ responses. In contrast in the AdCA trial, CHMI caused both pre-CHMI ELISpot IFN-γ and CD8+ T cell IFN-γ responses of the AdCA subjects to fall. We suggest that the falls in activities are due to migration of peripheral CD8+ T cells to the liver in response to developing liver stage parasites, and this fall, in the DNA/Ad trial, is masked in ELISpot responses of the non-protected subjects by rises in other immune cell types. In addition, CHMI caused falls in antibody activities of protected subjects, but rises in non-protected subjects in both trials to CSP, and dramatically in the AdCA trial to AMA1, reaching 380 μg/ml that is probably due to boosting by transient blood stage infection before chloroquine treatment. Taken together, these results further define differences in cellular responses between DNA/Ad and AdCA trials, and suggest that natural transmission may boost responses induced by these malaria vaccines especially when protection is not achieved.
a Naval Medical Research Center ; Silver Spring , MD USA.
Martha
M
Sedegah
a Naval Medical Research Center ; Silver Spring , MD USA.
Michael R
MR
Hollingdale
a Naval Medical Research Center ; Silver Spring , MD USA.
Fouzia
F
Farooq
a Naval Medical Research Center ; Silver Spring , MD USA.
Harini
H
Ganeshan
a Naval Medical Research Center ; Silver Spring , MD USA.
Maria
M
Belmonte
a Naval Medical Research Center ; Silver Spring , MD USA.
Jun
J
Huang
a Naval Medical Research Center ; Silver Spring , MD USA.
Esteban
E
Abot
a Naval Medical Research Center ; Silver Spring , MD USA.
Keith
K
Limbach
a Naval Medical Research Center ; Silver Spring , MD USA.
Ilin
I
Chuang
a Naval Medical Research Center ; Silver Spring , MD USA.
Cindy
C
Tamminga
a Naval Medical Research Center ; Silver Spring , MD USA.
Judith E
JE
Epstein
a Naval Medical Research Center ; Silver Spring , MD USA.
Eileen
E
Villasante
D062705:Adenovirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D058501:Enzyme-Linked Immunospot Assay; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000378:metabolism; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D062705:Adenovirus Vaccines; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C090077:apical membrane antigen I, Plasmodium; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma
AMA1; CHMI; CSP; DNA -prime; T cells; adenovirus-boost; antibody; efficacy; malaria; vaccine