use of Anthrax Vaccine in the united states recommendations of the advisory committee on immunization practices acip 2009

This report updates the 2009 recommendations from the CDC Advisory Committee on Immunization Practices (ACIP) regarding use of Anthrax Vaccine in the United States (Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of Anthrax Vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices [ACIP)], 2009. MMWR Recomm Rep 2010;59[No. RR-6]). The report 1) summarizes data on estimated efficacy in humans using a correlates of protection model and safety data published since the last ACIP review, 2) provides updated guidance for use of Anthrax Vaccine adsorbed (AVA) for preexposure prophylaxis (PrEP) and in conjunction with antimicrobials for postexposure prophylaxis (PEP), 3) provides updated guidance regarding PrEP vaccination of emergency and other responders, 4) summarizes the available data on an investigational Anthrax Vaccine (AV7909), and 5) discusses the use of Anthrax antitoxins for PEP.

Changes from previous guidance in this report include the following: 1) a booster dose of AVA for PrEP can be given every 3 years instead of annually to persons not at high risk for exposure to Bacillus anthracis who have previously received the initial AVA 3-dose priming and 2-dose booster series and want to maintain protection; 2) during a large-scale emergency response, AVA for PEP can be administered using an intramuscular route if the subcutaneous route of administration poses significant materiel, personnel, or clinical challenges that might delay or preclude vaccination; 3) recommendations on dose-sparing AVA PEP regimens if the Anthrax Vaccine supply is insufficient to vaccinate all potentially exposed persons; and 4) clarification on the duration of antimicrobial therapy when used in conjunction with Vaccine for PEP.

These updated recommendations can be used by health care providers and guide emergency preparedness officials and planners who are developing plans to provide Anthrax Vaccine, including preparations for a wide-area aerosol release of B. anthracis spores. The recommendations also provide guidance on dose-sparing options, if needed, to extend the supply of Vaccine to increase the number of persons receiving PEP in a mass casualty event.

antibody response to a delayed booster dose of Anthrax Vaccine and botulinum toxoid

Abstract We evaluated the prevalence and concentration of serum antibodies 18–24 months after primary inoculation with Anthrax and botulinum Vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these Vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with Anthrax Vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed Anthrax Vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18–24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18–24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02 IU/ml, and 97% responded with titers ≥0.25 IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other Vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of Anthrax Vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations.

Anthrax Vaccine short term safety experience in humans

Bacillus anthracisis the major terrorist and biological warfare agent of concern to civilian and military medical planners. The licensed Anthrax Vaccine, adsorbed (AVA) is believed to be an effective prophylactic medical countermeasure against this threat. Our objective in this report was to expand the safety database for this Vaccine by assessing data on self-reported, short-term safety of AVA during more than 25 years of use, measured by local and systemic adverse events temporally associated with the administration of AVA. A minority of AVA recipients reported systemic and injection site reactions. Females reported a higher incidence of injection site and systemic adverse events than males. Data show a difference in incidence of local reactions between lots. A prospective, randomized, placebo-controlled study to actively examine reactogenicity is needed to more completely define the extent and nature of reactions associated with receipt of AVA in humans as well as to confirm the gender lot differences in local reaction rates. © 2001 Published by Elsevier Science Ltd.

the role of hla dr dq haplotypes in variable antibody responses to Anthrax Vaccine adsorbed

Host genetic variation, particularly within the human leukocyte antigen (HLA) loci, reportedly mediates heterogeneity in immune response to certain Vaccines; however, no large study of genetic determinants of Anthrax Vaccine response has been described. We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA–DRB1, –DQA1, –DQB1, –DPB1) loci. The study included 794 European-Americans and 200 African-Americans participating in a 43-month, double-blind and placebo-controlled clinical trial of AVA (clinicaltrials.gov identifier NCT00119067). Among European-Americans, genes from tightly linked HLA–DRB1, –DQA1, –DQB1 haplotypes displayed significant overall associations with longitudinal variation in AbPA levels at 4, 8, 26 and 30 weeks from baseline in response to vaccination with three or four doses of AVA (global P=6.53 × 10−4). In particular, carriage of the DRB1–DQA1–DQB1 haplotypes *1501–*0102–*0602 (P=1.17 × 10−5), *0101–*0101–*0501 (P=0.009) and *0102–*0101–*0501 (P=0.006) was associated with significantly lower AbPA levels. In carriers of two copies of these haplotypes, lower AbPA levels persisted following subsequent vaccinations. No significant associations were observed amongst African-Americans or for any HLA class I allele/haplotype. Further studies will be required to replicate these findings and to explore the role of host genetic variation outside of the HLA region.

The Role of HLA DR-DQ Haplotypes in Variable Antibody Responses to Anthrax Vaccine Adsorbed

The role of HLA–DR–DQ haplotypes in variable antibody responses to Anthrax Vaccine Adsorbed

cpg oligonucleotides improve the protective immune response induced by the licensed Anthrax Vaccine

: Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants, improving the response elicited by a coadministered Vaccine. Combining CpG ODN with Anthrax Vaccine adsorbed (AVA, the licensed human Vaccine) increases the speed, magnitude, and avidity of the resultant antibody response. IgG Abs against Anthrax protective antigen (PA) protect mice, guinuea pigs, and rhesus macaques from infection.

cpg oligodeoxynucleotides adsorbed onto polylactide co glycolide microparticles improve the immunogenicity and protective activity of the licensed Anthrax Vaccine

To reduce the biothreat posed by Anthrax, efforts are under way to improve the protection afforded by vaccination. This work examines the ability of immunostimulatory CpG oligodeoxynucleotides (ODN) adsorbed onto cationic polylactide-co-glycolide (PLG) microparticles (CpG ODN-PLG) to accelerate and boost the protective immunity elicited by Anthrax Vaccine Adsorbed (AVA, the licensed human Anthrax Vaccine). The results indicate that coadministering CpG ODN-PLG with AVA induces a stronger and faster immunoglobulin G response against the protective antigen of Anthrax than AVA alone. Immunized mice were protected from lethal Anthrax challenge within 1 week of vaccination with CpG ODN-PLG plus AVA, with the level of protection correlating with serum immunoglobulin G anti-protective antigen titers.

development of an in vitro based potency assay for Anthrax Vaccine

Abstract The potency assay currently used to evaluate consistency of manufacture for the Anthrax Vaccine is contingent upon meeting specified parameters after statistical analysis of the percent survival and time to death of vaccinated guinea pigs after challenge with spores of a virulent strain of Bacillus anthracis. During the development of a new Anthrax Vaccine based upon recombinant protective antigen (rPA) adsorbed to aluminum hydroxide gel (Alhydrogel), we found that the serological response of female A/J mice, as measured by a quantitative anti-rPA IgG ELISA, may be an effective method to monitor a manufacturer’s consistency for rPA-based Vaccines. An advantage of the proposed in vitro-based potency assay is that it will not need stringent biosafety containment measures as required by the current guinea pig potency assay.