Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Abstract

A nthrax vaccine adsorbed (AVA; BioThrax; Emergent Bio Solutions Inc., Lansing, MI) is the only Food and Drug Administration (FDA)-approved vaccine in the United States for prevention of anthrax in humans. The primary immunogen in AVA is anthrax toxin protective antigen (PA). Serum anti-PA antibody levels are accurate immune correlates of protection in nonhuman primate (NHP) models of inhalation anthrax and for predicted probability of survival in humans (1-3). There is a significant lack of data in humans regarding the onset, duration, quantitative analysis, and functional activity of humoral antibody and cell-mediated immunity (CMI) responses following priming and boosting with AVA.In 2012, the preexposure schedule for AVA was approved as a priming series of three 0.5-ml intramuscular (IM) injections at 0, 1, and 6 months (3-IM) with subsequent boosters at 12 and 18 months and annually thereafter for those at continued risk of infection (http://www.fda.gov/BiologicsBloodVaccines/Vaccines /ApprovedProducts/ucm304758.htm; http://www.fda.gov /downloads/BiologicsBloodVaccines/BloodBloodProducts /ApprovedProducts/LicensedProductsBLAs/UCM074923 .pdf). In 2013, AVA received market approval in the European Union (EU) using a 3-IM priming series and 3-yearly booster schedule (http://emergentbiosolutions.com/sites/default/files /BioThrax_Germany.pdf).These recent changes in the FDA-approved priming schedule and route of administration for AVA and EU approval of an alternate schedule warranted detailed characterization of their immunological impact. Serological noninferiority analyses for peak anti-PA IgG and lethal toxin neutralization activity (TNA) in response to the 3-IM priming schedule and alternative booster schedules were reported previously, and the safety profile of AVA administered IM in humans was confirmed to be similar to that for other alum-containing vaccines (4-6). Less frequent AVA injection doses resulted in a reduction in some injection site adverse events (AEs), and IM administration resulted in reduced frequency, duration, and severity of AEs (5-11). The potential for increasing the intervals between booster doses requires an assessment of sustained antibody functional activity, CMI, and the ability to develop rapid protective anamnestic responses (5,6,12).In a rhesus macaque model of inhalation anthrax, the AVA

Characterization of the UK anthrax vaccine and human immunogenicity

“…Although there is evidence that anti-PA antibodies and TNA levels have good correlation in human studies, 7 , 42 , 43 strong correlation was not observed in this study, potentially due to the small sample size. Previous studies have shown that antibody and TNA levels can be highly variable in AVA and AVP vaccinees.…”

Recent progress in broadly neutralizing antibodies to HIV

“…We next sought to estimate the protection coverage of a vaccine that is capable of eliciting PGT121, PGDM1400 and VRC01. The concentration of the immunoglobulin IgG in human serum is approximately 10 mg/ml, and a serum concentration of 30 μg/ml, which is an approximate titer of 1:300, corresponds to a reasonable sustained vaccine-induced titer achieved via standard immunization protocols 93 . At this concentration, the protection coverage by most bnAbs increases, and if PGT121, PGDM1400 and VRC01 could be elicited at a serum concentration of 30 μg/ml for each Ab, then we project approximately 94% protection coverage (Fig.…”

“…Accordingly, we estimate PGT121 would provide 36% protection coverage if it were elicited by vaccination at a serum concentration of 15 μg/ml (on the basis of data for SHIV-SF162P3) and to provide 50% protection coverage if elicited at a concentration of 22 μg/ml (data for SHIV-AD8EO data). We also provide estimated protection coverage if each mAb or combinations of mAbs were elicited at a serum concentration of 30 μg/ml, as a reasonable sustained concentration of Abs elicited by vaccination 93 . In the plot, each symbol represents a unique SHIV isolate (194–200 isolates tested per Ab), with colors (key) indicating the epitope targeted by the Ab (along horizontal axis; SHIV below), and each symbol position represents the neutralization IC 50 in the TZM-bl assay (vertical axis).…”

Mechanisms of CXCL10 Antimicrobial Activity against Bacillus anthracis

“…It is administered in a series of five doses over 18 months, with a yearly booster after completion. There is evidence that three intramuscular doses are sufficient for protection for up to 3.5 years (27). Studies to evaluate the most effective vaccination schedule are ongoing (27).…”

“…There is evidence that three intramuscular doses are sufficient for protection for up to 3.5 years (27). Studies to evaluate the most effective vaccination schedule are ongoing (27). There has been some debate about the safety of the vaccine with reports of chronic adverse effects such as fever, malaise, and joint pain (28).…”