A three-dose intramuscular injection schedule of anthrax vaccine adsorbed generates sustained humoral and cellular immune responses to protective antigen and provides long-term protection against inhalation anthrax in rhesus macaques.
Clin Vaccine Immunol
; 19(11): 1730-45, 2012 Nov.
Article
in En
| MEDLINE
| ID: mdl-22933399
ABSTRACT
A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 110 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 15 AVA or following two injections of diluted vaccine (110, 120, or 140 AVA). Anti-PA and TNA were highly correlated (overall r(2) = 0.89 for log(10)-transformed data). Peak responses were seen at 6.5 months. In general, with the exception of animals receiving 140 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 120 AVA), and through 50.5 months for the HuAVA and 15 and 110 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4(+) cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 15 and 120 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 120 AVA and 52 months for 110 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses.
Full text:
1
Collection:
01-internacional
Health context:
2_ODS3
/
3_ND
/
4_TD
Database:
MEDLINE
Main subject:
Respiratory Tract Infections
/
Bacterial Toxins
/
T-Lymphocytes
/
Vaccination
/
Anthrax Vaccines
/
Anthrax
/
Antibodies, Bacterial
/
Antigens, Bacterial
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Clin Vaccine Immunol
Year:
2012
Document type:
Article