Immunogenicity of recombinant protective antigen and efficacy against aerosol challenge with anthrax.
Immunization with a recombinant form of the protective antigen (rPA) from Bacillus anthracis has been carried out with rhesus macaques. Rhesus macaques immunized with 25 mug or more of B. subtilis-expressed rPA bound to alhydrogel had a significantly increased immunoglobulin G (IgG) response to rPA compared with macaques receiving the existing licensed vaccine from the United Kingdom (anthrax vaccine precipitated [AVP]), although the isotype profile was unchanged, with bias towards the IgG1 and IgG2 subclasses. Immune macaque sera from all immunized groups contained toxin-neutralizing antibody and recognized all the domains of PA. While the recognition of the N terminus of PA (domains 1 to 3) was predominant in macaques immunized with the existing vaccines (AVP and the U.S. vaccine anthrax vaccine adsorbed), macaques immunized with rPA recognized the N- and C-terminal domains of PA. Antiserum derived from immunized macaques protected macrophages in vitro against the cytotoxic effects of lethal toxin. Passive transfer of IgG purified from immune macaque serum into naive A/J mice conferred protection against challenge with B. anthracis in a dose-related manner. The protection conferred by passive transfer of 500 mug macaque IgG correlated significantly (P = 0.003; r = 0.4) with the titers of neutralizing antibody in donor macaques. Subsequently, a separate group of rhesus macaques immunized with 50 mug of Escherichia coli-derived rPA adsorbed to alhydrogel was fully protected against a target dose of 200 50% lethal doses of aerosolized B. anthracis. These data provide some preliminary evidence for the existence of immune correlates of protection against anthrax infection in rhesus macaques immunized with rPA.
Williamson
E D
ED
Defence Science and Technology Laboratory Porton Down, Salisbury, Wilts. SP4 0JQ, United Kingdom. dewilliamson@dstl.gov.uk
Hodgson
I
I
Walker
N J
NJ
Topping
A W
AW
Duchars
M G
MG
Mott
J M
JM
Estep
J
J
Lebutt
C
C
Flick-Smith
H C
HC
Jones
H E
HE
Li
H
H
Quinn
C P
CP
D000281:Administration, Intranasal; D000336:Aerosols; D000818:Animals; D000881:Anthrax / Q000276:immunology*; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001408:Bacillus anthracis / Q000235:genetics / Q000276:immunology*; D001412:Bacillus subtilis / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008253:Macaca mulatta; D051379:Mice; D008805:Mice, Inbred A; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000336:Aerosols; D022122:Anthrax Vaccines; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D011994:Recombinant Proteins