Ag85B-ESAT-6 adjuvanted with IC31® promotes strong and long-lived Mycobacterium tuberculosis specific T cell responses in volunteers with previous BCG vaccination or tuberculosis infection.
New TB vaccines are urgently needed because of the apparent lack of effect of the BCG vaccine on rates of adult contagious pulmonary tuberculosis and the risk of disseminated BCG disease in immunocompromised individuals. Since BCG appears to protect children, the primary target for vaccine development is a booster vaccine for adults but such vaccines ideally need to be able to efficiently prime mycobacterially naïve individuals as well as boost individuals previously vaccinated with BCG and those latently infected with TB. Protective immunity against Mycobacterium tuberculosis depends mainly on the generation of a Th1-type cellular immune response characterized by interferon-gamma (IFN-γ) production. In the present study, we monitored safety and IFN-γ responses in healthy BCG-vaccinated and prior or latently TB-infected individuals receiving a novel vaccine composed of the fusion protein Ag85B-ESAT-6 combined with the adjuvant IC31(®), administered at 0 and 2 months. Vaccination caused few local or systemic adverse effects besides transient soreness at the injection site, but it elicited strong antigen-specific T cell responses against Ag85B-ESAT-6 and both the Ag85B and ESAT-6 components, that could be augmented by second vaccination. The strong responses persisted through 32 weeks of follow-up, indicating the induction of a persistent memory response in the vaccine recipients.
Leiden University Medical Center (LUMC), Department of Infectious Diseases, Leiden, The Netherlands. j.t.van dissel@lumc.nl
Jaap T
JT
van Dissel
Darius
D
Soonawala
Simone A
SA
Joosten
Corine
C
Prins
Sandra M
SM
Arend
Peter
P
Bang
Pernille Nyholm
PN
Tingskov
Karen
K
Lingnau
Jan
J
Nouta
Søren T
ST
Hoff
Ida
I
Rosenkrands
Ingrid
I
Kromann
Tom H M
TH
Ottenhoff
T Mark
TM
Doherty
Peter
P
Andersen
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000008:administration & dosage; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology; D055985:Latent Tuberculosis / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult
C557979:Ag85B-ESAT-6 fusion antigen; D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D004338:Drug Combinations; C544002:IC31 adjuvant; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma