The Experts below are selected from a list of 456 Experts worldwide ranked by ideXlab platform

Michael M. Mcneil - One of the best experts on this subject based on the ideXlab platform.

  • Recent developments in the understanding and use of Anthrax Vaccine Adsorbed: achieving more with less
    Expert review of vaccines, 2016
    Co-Authors: Michael M. Mcneil
    Abstract:

    Anthrax Vaccine Adsorbed (AVA, BioThrax™) is the only Food and Drug Administration (FDA) approved Vaccine for the prevention of Anthrax in humans. Recent improvements in pre-exposure prophylaxis (PrEP) use of AVA include intramuscular (IM) administration and simplification of the priming series to three doses over 6 months. Administration IM markedly reduced the frequency, severity and duration of injection site reactions. Refinement of animal models for inhalation Anthrax, identification of immune correlates of protection and cross-species modeling have created opportunities for reductions in the PrEP booster schedule and were pivotal in FDA approval of a post-exposure prophylaxis (PEP) indication. Clinical and nonclinical studies of accelerated PEP schedules and divided doses may provide prospects for shortening the PEP antimicrobial treatment period. These data may assist in determining feasibility of expanded coverage in a large-scale emergency when Vaccine demand may exceed availability. Enhancements to the AVA formulation may broaden the Vaccine's PEP application.

  • Anthrax Vaccine and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus in the U.S. Military: A Case-Control Study.
    Military medicine, 2016
    Co-Authors: Barbara H. Bardenheier, Jonathan Duffy, Susan K. Duderstadt, Jay B. Higgs, Michael P. Keith, Patricia J. Papadopoulos, William R. Gilliland, Michael M. Mcneil
    Abstract:

    U.S. military personnel assigned to areas deemed to be at high risk for Anthrax attack receive Anthrax Vaccine Adsorbed (AVA). Few cases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been reported in persons who received AVA. Using a matched case-control study design, we assessed the relationship of RA and SLE with AVA vaccination using the Defense Medical Surveillance System. We identified potential cases using International Classification of Diseases, 9th Revision, Clinical Modification codes and confirmed cases with medical record review and rheumatologist adjudication. Using conditional logistic regression, we estimated odds ratios (OR) for AVA exposure during time intervals ranging from 90 to 1,095 days before disease onset. Among 77 RA cases, 13 (17%) had ever received AVA. RA cases were no more likely than controls to have received AVA when looking back 1,095 days (OR: 1.03; 95% confidence interval [CI]: 0.48-2.19) but had greater odds of exposure in the prior 90 days (OR: 3.93; 95% CI: 1.08-14.27). Among the 39 SLE cases, 5 (13%) had ever received AVA; no significant difference in receipt of AVA was found when compared with controls (OR: 0.91; 95% CI: 0.26-3.25). AVA was associated with recent onset RA, but did not increase the risk of developing RA in the long term.

  • evaluation of sex race body mass index and pre vaccination serum progesterone levels and post vaccination serum anti Anthrax protective immunoglobulin g on injection site adverse events following Anthrax Vaccine Adsorbed ava in the cdc ava human clin
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Scott Parker, Gregory A Poland, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Abstract Background Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.

  • Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-Anthrax protective immunoglobulin G on injection site adverse events following Anthrax Vaccine Adsorbed (AVA) in the CDC AVA human
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Gregory A Poland, Wendy A Keitel, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. Published by Elsevier Ltd.

  • assessing agreement of repeated binary measurements with an application to the cdc s Anthrax Vaccine clinical trial
    The International Journal of Biostatistics, 2013
    Co-Authors: Charles E. Rose, Gregory A Poland, Robert M. Jacobson, Brock Stewart, Harry L. Keyserling, Michael Haber, Josep L Carrasco, Michael M. Mcneil
    Abstract:

    Cohen’s kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. However, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. This study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions and discusses under which condition we should use the most appropriate method in practice. These approaches are illustrated using data from the CDC Anthrax Vaccine Adsorbed (AVA) human clinical trial comparing the agreement for two solicited adverse events after AVA between the 1–3 day in-clinic medical record and the patient’s diary on the same day. We hope this article can inspire researchers to choose the most appropriate method to assess agreement for their own study with longitudinal binary data.

B E Ivins - One of the best experts on this subject based on the ideXlab platform.

  • An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals ☆
    Vaccine, 2008
    Co-Authors: John Hewetson, B E Ivins, Phillip R. Pittman, Stephen F. Little, Sarah L Norris, Wendy M Johnson, J. Edward Brown, Carl J Nielsen
    Abstract:

    Samples of human plasma from Anthrax Vaccine Adsorbed (AVA, BioThrax)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of Anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 microg of anti-PA IgG was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). Mice showed significant survival (p

  • An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals ☆
    Vaccine, 2008
    Co-Authors: John Hewetson, B E Ivins, Phillip R. Pittman, Stephen F. Little, Sarah L Norris, Wendy M Johnson, J. Edward Brown, Carl J Nielsen
    Abstract:

    Samples of human plasma from Anthrax Vaccine Adsorbed (AVA, BioThrax™)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of Anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 μg of anti-PA IgG was 134 μg/ml, declining to 91 μg/ml at 72 h (half-life = 101.7 h). Mice showed significant survival (p ≤ 0.001) after injection of serial dilutions up to 1:4 of the standard plasma and challenged with 100 LD50. Similarly, mice injected with the standard anti-AVA plasma and challenged up to 5 days post-treatment also survived (p ≤ 0.001). Using a cohort of human plasma to measure passive protection, the best correlation between passive protection and an in vitro assay was found to be with the quantitative toxin neutralization assay (minimum fold increase in odds of survival: 2.71, p = 0.0062). These results demonstrate a reliable in vivo neutralization method that correlates with standard in vitro measures of neutralizing antibody levels in plasma from individuals vaccinated with the standard Anthrax Vaccine. This analytical method may provide additional opportunities to compare the efficacy of improved Anthrax Vaccines with the licensed Vaccine.

  • cpg oligonucleotides improve the protective immune response induced by the licensed Anthrax Vaccine
    Annals of the New York Academy of Sciences, 2006
    Co-Authors: Dennis M. Klinman, B E Ivins
    Abstract:

    : 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
    Infection and Immunity, 2005
    Co-Authors: Ihsan Gursel, B E Ivins, Jeffrey B Ulmer, Derek Ohagan, Manmohan Singh, Dennis M. Klinman
    Abstract:

    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.

  • Anthrax Vaccine efficacy in golden Syrian hamsters.
    Vaccine, 2002
    Co-Authors: P F Fellows, M K Linscott, P Gibbs, S F Little, B E Ivins
    Abstract:

    The efficacy of a licensed human Anthrax Vaccine (Anthrax Vaccine Adsorbed, AVA) was tested in golden Syrian hamsters against a virulent Bacillus anthracis spore challenge. Groups of golden Syrian hamsters were vaccinated at either 0 and 4 weeks or 0, 4 and 8 weeks, then challenged subcutaneously (s.c.) at 10 weeks with spores of various B. anthracis isolates. Although ELISA and toxin neutralization assays demonstrated high titers, none of the AVA-vaccinated hamsters were protected from challenge or demonstrated a significantly extended time to death compared to that of control animals. The results of the study demonstrate that the golden Syrian hamster is not an appropriate model for investigating human Anthrax Vaccine efficacy.

Gregory A Poland - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of sex race body mass index and pre vaccination serum progesterone levels and post vaccination serum anti Anthrax protective immunoglobulin g on injection site adverse events following Anthrax Vaccine Adsorbed ava in the cdc ava human clin
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Scott Parker, Gregory A Poland, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Abstract Background Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.

  • Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-Anthrax protective immunoglobulin G on injection site adverse events following Anthrax Vaccine Adsorbed (AVA) in the CDC AVA human
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Gregory A Poland, Wendy A Keitel, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. Published by Elsevier Ltd.

  • effect of reduced dose schedules and intramuscular injection of Anthrax Vaccine Adsorbed on immunological response and safety profile a randomized trial
    Vaccine, 2014
    Co-Authors: Jennifer G Wright, Scott Parker, Gregory A Poland, Robert M. Jacobson, Charles E. Rose, Janiine Babcock, Brian D. Plikaytis, Hana El M Sahly, Harry L. Keyserling
    Abstract:

    Abstract Objective We evaluated an alternative administration route, reduced schedule priming series, and increased intervals between booster doses for Anthrax Vaccine Adsorbed (AVA). AVA's originally licensed schedule was 6 subcutaneous (SQ) priming injections administered at months (m) 0, 0.5, 1, 6, 12 and 18 with annual boosters; a simpler schedule is desired. Methods Through a multicenter randomized, double blind, non-inferiority Phase IV human clinical trial, the originally licensed schedule was compared to four alternative and two placebo schedules. 8-SQ group participants received 6 SQ injections with m30 and m42 “annual” boosters; participants in the 8-IM group received intramuscular (IM) injections according to the same schedule. Reduced schedule groups (7-IM, 5-IM, 4-IM) received IM injections at m0, m1, m6; at least one of the m0.5, m12, m18, m30 Vaccine doses were replaced with saline. All reduced schedule groups received a m42 booster. Post-injection blood draws were taken two to four weeks following injection. Non-inferiority of the alternative schedules was compared to the 8-SQ group at m2, m7, and m43. Reactogenicity outcomes were proportions of injection site and systemic adverse events (AEs). Results The 8-IM group's m2 response was non-inferior to the 8-SQ group for the three primary endpoints of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer, and proportion of responders with a 4-fold rise in titer. At m7 anti-PA IgG GMCs for the three reduced dosage groups were non-inferior to the 8-SQ group GMCs. At m43, 8-IM, 5-IM, and 4-IM group GMCs were superior to the 8-SQ group. Solicited injection site AEs occurred at lower proportions in the IM group compared to SQ. Route of administration did not influence the occurrence of systemic AEs. A 3 dose IM priming schedule with doses administered at m0, m1, and m6 elicited long term immunological responses and robust immunological memory that was efficiently stimulated by a single booster vaccination at 42 months. Conclusions A priming series of 3 intramuscular doses administered at m0, m1, and m6 with a triennial booster was non-inferior to more complex schedules for achieving antibody response.

  • assessing agreement of repeated binary measurements with an application to the cdc s Anthrax Vaccine clinical trial
    The International Journal of Biostatistics, 2013
    Co-Authors: Charles E. Rose, Gregory A Poland, Robert M. Jacobson, Brock Stewart, Harry L. Keyserling, Michael Haber, Josep L Carrasco, Michael M. Mcneil
    Abstract:

    Cohen’s kappa coefficient, which was introduced in 1960, serves as the most widely employed coefficient to assess inter-observer agreement for categorical outcomes. However, the original kappa can only be applied to cross-sectional binary measurements and, therefore, cannot be applied in the practical situation when the observers evaluate the same subjects at repeated time intervals. This study summarizes six methods of assessing agreement of repeated binary outcomes under different assumptions and discusses under which condition we should use the most appropriate method in practice. These approaches are illustrated using data from the CDC Anthrax Vaccine Adsorbed (AVA) human clinical trial comparing the agreement for two solicited adverse events after AVA between the 1–3 day in-clinic medical record and the patient’s diary on the same day. We hope this article can inspire researchers to choose the most appropriate method to assess agreement for their own study with longitudinal binary data.

  • human leukocyte antigens and cellular immune responses to Anthrax Vaccine Adsorbed
    Infection and Immunity, 2013
    Co-Authors: Inna G Ovsyannikova, Nicholas M. Pajewski, Richard A Kaslow, Robert M. Jacobson, Shane V Pankratz, Robert A Vierkant, Gregory A Poland
    Abstract:

    Interindividual variations in Vaccine-induced immune responses are in part due to host genetic polymorphisms in the human leukocyte antigen (HLA) and other gene families. This study examined associations between HLA genotypes, haplotypes, and homozygosity and protective antigen (PA)-specific cellular immune responses in healthy subjects following immunization with Anthrax Vaccine Adsorbed (AVA). While limited associations were observed between individual HLA alleles or haplotypes and variable lymphocyte proliferative (LP) responses to AVA, analyses of homozygosity supported the hypothesis of a “heterozygote advantage.” Individuals who were homozygous for any HLA locus demonstrated significantly lower PA-specific LP than subjects who were heterozygous at all eight loci (median stimulation indices [SI], 1.84 versus 2.95, P = 0.009). Similarly, we found that class I (HLA-A) and class II (HLA-DQA1 and HLA-DQB1) homozygosity was significantly associated with an overall decrease in LP compared with heterozygosity at those three loci. Specifically, individuals who were homozygous at these loci had significantly lower PA-specific LP than subjects heterozygous for HLA-A (median SI, 1.48 versus 2.13, P = 0.005), HLA-DQA1 (median SI, 1.75 versus 2.11, P = 0.007), and HLA-DQB1 (median SI, 1.48 versus 2.13, P = 0.002) loci, respectively. Finally, homozygosity at an increasing number (≥4) of HLA loci was significantly correlated with a reduction in LP response (P < 0.001) in a dose-dependent manner. Additional studies are needed to reproduce these findings and determine whether HLA-heterozygous individuals generate stronger cellular immune response to other virulence factors (Bacillus anthracis LF and EF) than HLA-homozygous subjects.

Stacey W. Martin - One of the best experts on this subject based on the ideXlab platform.

  • evaluation of sex race body mass index and pre vaccination serum progesterone levels and post vaccination serum anti Anthrax protective immunoglobulin g on injection site adverse events following Anthrax Vaccine Adsorbed ava in the cdc ava human clin
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Scott Parker, Gregory A Poland, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Abstract Background Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. Methods We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n = 1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n = 227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Results Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Conclusions Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants.

  • Evaluation of sex, race, body mass index and pre-vaccination serum progesterone levels and post-vaccination serum anti-Anthrax protective immunoglobulin G on injection site adverse events following Anthrax Vaccine Adsorbed (AVA) in the CDC AVA human
    Vaccine, 2014
    Co-Authors: Tracy Pondo, Gregory A Poland, Wendy A Keitel, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Michael M. Mcneil
    Abstract:

    Anthrax Vaccine Adsorbed (AVA) administered intramuscularly (IM) results in fewer adverse events (AEs) than subcutaneous (SQ) administration. Women experience more AEs than men. Antibody response, female hormones, race, and body mass index (BMI) may contribute to increased frequency of reported injection site AEs. We analyzed data from the CDC AVA human clinical trial. This double blind, randomized, placebo controlled trial enrolled 1563 participants and followed them through 8 injections (AVA or placebo) over a period of 42 months. For the trial's vaccinated cohort (n=1267), we used multivariable logistic regression to model the effects of study group (SQ or IM), sex, race, study site, BMI, age, and post-vaccination serum anti-PA IgG on occurrence of AEs of any severity grade. Also, in a women-only subset (n=227), we assessed effect of pre-vaccination serum progesterone level and menstrual phase on AEs. Participants who received SQ injections had significantly higher proportions of itching, redness, swelling, tenderness and warmth compared to the IM study group after adjusting for other risk factors. The proportions of redness, swelling, tenderness and warmth were all significantly lower in blacks vs. non-black participants. We found arm motion limitation, itching, pain, swelling and tenderness were more likely to occur in participants with the highest anti-PA IgG concentrations. In the SQ study group, redness and swelling were more common for obese participants compared to participants who were not overweight. Females had significantly higher proportions of all AEs compared to males. Menstrual phase was not associated with any AEs. Female and non-black participants had a higher proportion of AVA associated AEs and higher anti-PA IgG concentrations. Antibody responses to other Vaccines may also vary by sex and race. Further studies may provide better understanding for higher proportions of AEs in women and non-black participants. Published by Elsevier Ltd.

  • Health-related quality of life in the CDC Anthrax Vaccine Adsorbed Human Clinical Trial.
    Vaccine, 2012
    Co-Authors: Brock Stewart, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Jerome I. Tokars, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Gregory A Poland
    Abstract:

    Abstract Background After the Department of Defense implemented a mandatory Anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current Anthrax Vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants’ quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination. Methods 1562 trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses. Results Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups. Conclusions These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period.

  • Health-related quality of life in the CDC Anthrax Vaccine Adsorbed Human Clinical Trial.
    Vaccine, 2012
    Co-Authors: Brock Stewart, Wendy A Keitel, Scott D. Parker, Robert M. Jacobson, Charles E. Rose, Jerome I. Tokars, Stacey W. Martin, Harry L. Keyserling, Janiine Babcock, Gregory A Poland
    Abstract:

    After the Department of Defense implemented a mandatory Anthrax vaccination program in 1998 concerns were raised about potential long-term safety effects of the current Anthrax Vaccine. The CDC multicenter, randomized, double-blind, placebo-controlled Anthrax Vaccine Adsorbed (AVA) Human Clinical Trial to evaluate route change and dose reduction collected data on participants' quality of life. Our objective is to assess the association between receipt of AVA and changes in health-related quality of life, as measured by the SF-36 health survey (Medical Outcomes Trust, Boston, MA), over 42 months after vaccination. 1562 trial participants completed SF-36v2 health surveys at 0, 12, 18, 30 and 42 months. Physical and mental summary scores were obtained from the survey results. We used Generalized Estimating Equations (GEE) analyses to assess the association between physical and mental score difference from baseline and seven study groups receiving either AVA at each dose, saline placebo at each dose, or a reduced AVA schedule substituting saline placebo for some doses. Overall, mean physical and mental scores tended to decrease after baseline. However, we found no evidence that the score difference from baseline changed significantly differently between the seven study groups. These results do not favor an association between receipt of AVA and an altered health-related quality of life over a 42-month period. Published by Elsevier Ltd.

  • effects of a reduced dose schedule and intramuscular administration of Anthrax Vaccine Adsorbed on immunogenicity and safety at 7 months a randomized trial
    JAMA, 2008
    Co-Authors: Nina Marano, Vera A. Semenova, Charles E. Rose, Stacey W. Martin, Han Li, Brian D. Plikaytis, Sandra K Martin, Alison E Freeman, Mark J Mulligan, Scott Parker
    Abstract:

    Context In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of Anthrax Vaccine Adsorbed (AVA). Objective To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (SQ) to intramuscular (IM) and omitting the week 2 dose from the licensed schedule. Design, Setting, and Participants Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002). Intervention Healthy adults received AVA by the SQ (reference group) or IM route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals. Main Outcome Measures Noninferiority at week 8 and month 7 of anti–protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4×R). Reactogenicity outcomes were proportions of injection site and systemic AEs. Results At week 8, the 4-IM group (GMC, 90.8 μg/mL; GMT, 1114.8; %4×R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 μg/mL; GMT, 1315.4; %4×R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4×R (GMC, 52.2 μg/mL; GMT, 650.6; %4×R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P  Conclusions The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067

Phillip R. Pittman - One of the best experts on this subject based on the ideXlab platform.

  • Anthrax Vaccine Adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.
    Vaccine, 2014
    Co-Authors: Phillip R. Pittman, M.a. Cavicchia, J.l. Kingsbury, J.g. Barrera-oro, Lawrence Korman, Xiaofei Quinn, Trevor J. Schmader, N.a. Johnson, Manmohan V. Ranadive
    Abstract:

    Abstract Whether to restart or continue the series when Anthrax Vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the Anthrax Vaccine Adsorbed (AVA) (Biothrax®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (p

  • Effect of delayed Anthrax Vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.
    Vaccine, 2013
    Co-Authors: Phillip R. Pittman, Xiaofei Quinn, Trevor J. Schmader, Diana Fisher, Julio G. Barrera-oro
    Abstract:

    Abstract We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of Anthrax Vaccine Adsorbed (AVA, BioThrax ® ) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18–24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% ( P P B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series.

  • An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals ☆
    Vaccine, 2008
    Co-Authors: John Hewetson, B E Ivins, Phillip R. Pittman, Stephen F. Little, Sarah L Norris, Wendy M Johnson, J. Edward Brown, Carl J Nielsen
    Abstract:

    Samples of human plasma from Anthrax Vaccine Adsorbed (AVA, BioThrax™)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of Anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 μg of anti-PA IgG was 134 μg/ml, declining to 91 μg/ml at 72 h (half-life = 101.7 h). Mice showed significant survival (p ≤ 0.001) after injection of serial dilutions up to 1:4 of the standard plasma and challenged with 100 LD50. Similarly, mice injected with the standard anti-AVA plasma and challenged up to 5 days post-treatment also survived (p ≤ 0.001). Using a cohort of human plasma to measure passive protection, the best correlation between passive protection and an in vitro assay was found to be with the quantitative toxin neutralization assay (minimum fold increase in odds of survival: 2.71, p = 0.0062). These results demonstrate a reliable in vivo neutralization method that correlates with standard in vitro measures of neutralizing antibody levels in plasma from individuals vaccinated with the standard Anthrax Vaccine. This analytical method may provide additional opportunities to compare the efficacy of improved Anthrax Vaccines with the licensed Vaccine.

  • An in vivo passive protection assay for the evaluation of immunity in AVA-vaccinated individuals ☆
    Vaccine, 2008
    Co-Authors: John Hewetson, B E Ivins, Phillip R. Pittman, Stephen F. Little, Sarah L Norris, Wendy M Johnson, J. Edward Brown, Carl J Nielsen
    Abstract:

    Samples of human plasma from Anthrax Vaccine Adsorbed (AVA, BioThrax)-vaccinated individuals were used to demonstrate passive protection of A/J mice from a lethal challenge with the Sterne strain of Anthrax bacteria. The maximum concentration of human anti-protective antigen IgG in mouse sera 24 h after injection of 260 microg of anti-PA IgG was 134 microg/ml, declining to 91 microg/ml at 72 h (half-life=101.7 h). Mice showed significant survival (p

  • patterns of antibody response in humans to the Anthrax Vaccine Adsorbed ava primary six dose series
    Vaccine, 2006
    Co-Authors: Phillip R. Pittman, Timothy L Cannon, Sarah L Norris, David Bedwell, Kelly T Mckee
    Abstract:

    The antibody profile during and after the six-dose primary vaccination series with Anthrax Vaccine Adsorbed (AVA, Biothrax TM )w as characterized in 86 human volunteers. Ninety-three percent of recipients developed IgG antibodies to Bacillus anthracis protective antigen (PA) after two doses, and 100% were seropositive after dose #3. Geometric mean concentrations (GMC) of IgG to PA measured before and after each dose were significantly lower after injection #3 (peak GMC = 146.65g/mL, trough GMC = 15.16g/mL) than after injections #4 (peak GMC = 430.46g/mL, trough GMC = 94.57g/mL), #5 (peak GMC = 415.05g/mL, trough GMC = 81.94g/mL), or #6 (peak GMC = 401.16g/mL, trough GMC = 96.19g/mL) (p ≤ 0.0001 for each); but not between injections #4 and #5, #5 and #6, or #4 and #6 (p ≥ 0.7923 for each). Decay rates for IgG to PA were significantly faster after injection #3 (half life [T1/2] = 39.21 days) than after injections #4 (T1/2 = 72.03 days), #5 (T1/2 = 70.14 days), and #6 (T1/2 = 74.59 days) (p ≤ 0.0282 for each). Toxin neutralizing assay (TNA) antibody patterns generally paralleled those for IgG to PA. The 6-month dose in the AVA primary series appears to be critical in sustaining IgG to PA