Addition of CpG ODN to recombinant Pseudomonas aeruginosa ExoProtein A conjugates of AMA1 and Pfs25 greatly increases the number of responders.
Both the blood-stage protein apical membrane antigen 1 (AMA1) and the 25-kDa sexual-stage protein (Pfs25) of Plasmodium falciparum are two leading candidates in malarial vaccine development. We have previously demonstrated that conjugation of these malarial antigens to recombinant Pseudomonas aeruginosa ExoProtein A (rEPA) significantly increased the mean-specific functional antibody responses in mice; however, some mice responded poorly and were unable to demonstrate a functional response. We hypothesized that the immunogenicities of these two malarial antigens could be further enhanced by the inclusion of a CpG oligodeoxynucleotide in the formulation. Mice were immunized with either rEPA-conjugated or unconjugated AMA1 and Pfs25 formulated on Alhydrogel with or without the addition of CPG 7909. Mice received the formulations on days 0 and 28, and mouse sera were collected on day 42. ELISA analyses on these sera showed that the addition of CPG 7909 to AMA1-rEPA and Pfs25-rEPA formulated on Alhydrogel induced significantly higher mean antibody titers than the formulations without CPG 7909, and led to a mixed Th1/Th2 response as demonstrated by the production of mouse IgG1 and IgG2a subclasses. The presence of CPG 7909 in the formulations of both conjugated antigens greatly increased the proportion of responders with antibody titers sufficient to inhibit blood-stage parasite growth in vitro or block transmission of sexual-stage parasites to mosquitoes. The results obtained in this study indicate the potential use of a combination strategy to increase the number of responders to malarial antigens in humans.
Qian
Feng
F
Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Rausch
Kelly M
KM
Muratova
Olga
O
Zhou
Hong
H
Song
Guanhong
G
Diouf
Ababacar
A
Lambert
Lynn
L
Narum
David L
DL
Wu
Yimin
Y
Saul
Allan
A
Miller
Louis H
LH
Long
Carole A
CA
Mullen
Gregory E D
GE
D000276:Adjuvants, Immunologic; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C071284:Pfs25 protein, Plasmodium falciparum; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D000536:Aluminum Hydroxide