Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: A randomized, double-blinded, controlled, multicenter trial

Geoffrey J. Gorse, Wendy Keitel, Harry Keyserling, David N. Taylor, Michael Lock, Katia Alves, Julie Kenner, Lynne Deans, Marc Gurwith

Research output: Contribution to journalArticle

Abstract

Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p <0.001) and the second (84.2% versus 35.4%; p <0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

Original languageEnglish (US)
Pages (from-to)5950-5959
Number of pages10
JournalVaccine
Volume24
Issue number33-34
DOIs
StatePublished - Aug 14 2006
Externally publishedYes

Fingerprint

Anthrax Vaccines
Multicenter Studies
anthrax
Vaccination
vaccination
immune response
vaccines
Antigens
dosage
neutralization
toxins
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay
injection
Aluminum Hydroxide
aluminum hydroxide
headache
Injections
antibodies
adjuvants

Keywords

  • Anthrax vaccines
  • Clinical trial phase I
  • Immunogenicity
  • Recombinant vaccines
  • Safety

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Virology
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)

Cite this

Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine : A randomized, double-blinded, controlled, multicenter trial. / Gorse, Geoffrey J.; Keitel, Wendy; Keyserling, Harry; Taylor, David N.; Lock, Michael; Alves, Katia; Kenner, Julie; Deans, Lynne; Gurwith, Marc.

In: Vaccine, Vol. 24, No. 33-34, 14.08.2006, p. 5950-5959.

Research output: Contribution to journalArticle

Gorse, GJ, Keitel, W, Keyserling, H, Taylor, DN, Lock, M, Alves, K, Kenner, J, Deans, L & Gurwith, M 2006, 'Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: A randomized, double-blinded, controlled, multicenter trial', Vaccine, vol. 24, no. 33-34, pp. 5950-5959. https://doi.org/10.1016/j.vaccine.2006.05.044
Gorse, Geoffrey J. ; Keitel, Wendy ; Keyserling, Harry ; Taylor, David N. ; Lock, Michael ; Alves, Katia ; Kenner, Julie ; Deans, Lynne ; Gurwith, Marc. / Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine : A randomized, double-blinded, controlled, multicenter trial. In: Vaccine. 2006 ; Vol. 24, No. 33-34. pp. 5950-5959.
@article{e975d4e3e2714a6f909bcbac53122c65,
title = "Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine: A randomized, double-blinded, controlled, multicenter trial",
abstract = "Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7{\%} versus 44.4{\%}; p <0.001) and the second (84.2{\%} versus 35.4{\%}; p <0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4{\%} versus 15.8{\%}; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.",
keywords = "Anthrax vaccines, Clinical trial phase I, Immunogenicity, Recombinant vaccines, Safety",
author = "Gorse, {Geoffrey J.} and Wendy Keitel and Harry Keyserling and Taylor, {David N.} and Michael Lock and Katia Alves and Julie Kenner and Lynne Deans and Marc Gurwith",
year = "2006",
month = "8",
day = "14",
doi = "10.1016/j.vaccine.2006.05.044",
language = "English (US)",
volume = "24",
pages = "5950--5959",
journal = "Vaccine",
issn = "0264-410X",
publisher = "Elsevier BV",
number = "33-34",

}

TY - JOUR

T1 - Immunogenicity and tolerance of ascending doses of a recombinant protective antigen (rPA102) anthrax vaccine

T2 - A randomized, double-blinded, controlled, multicenter trial

AU - Gorse, Geoffrey J.

AU - Keitel, Wendy

AU - Keyserling, Harry

AU - Taylor, David N.

AU - Lock, Michael

AU - Alves, Katia

AU - Kenner, Julie

AU - Deans, Lynne

AU - Gurwith, Marc

PY - 2006/8/14

Y1 - 2006/8/14

N2 - Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p <0.001) and the second (84.2% versus 35.4%; p <0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

AB - Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75 μg of rPA102 in 82.5 μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p <0.001) and the second (84.2% versus 35.4%; p <0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p = 0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75 μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75 μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response.

KW - Anthrax vaccines

KW - Clinical trial phase I

KW - Immunogenicity

KW - Recombinant vaccines

KW - Safety

UR - http://www.scopus.com/inward/record.url?scp=33746058634&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33746058634&partnerID=8YFLogxK

U2 - 10.1016/j.vaccine.2006.05.044

DO - 10.1016/j.vaccine.2006.05.044

M3 - Article

C2 - 16797805

AN - SCOPUS:33746058634

VL - 24

SP - 5950

EP - 5959

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 33-34

ER -