Current State of Anthrax Vaccines and Key R&D Gaps Moving Forward

A licensed anthrax vaccine has been available for pre-exposure prophylaxis in the United States since 1970, and it was approved for use as a post-exposure prophylaxis, in combination with antibiotic treatment, in 2015. A variety of other vaccines are available in other nations, approved under various regulatory frameworks. However, investments in anthrax vaccines continue due to the severity of the threat posed by this bacterium, as both a naturally occurring pathogen and the potential for use as a bioweapon. In this review, we will capture the current landscape of anthrax vaccine development, focusing on those lead candidates in clinical development. Although approved products are available, a robust pipeline of candidate vaccines are still in development to try to address some of the key research gaps in the anthrax vaccine field. We will then highlight some of the most pressing needs in terms of anthrax vaccine research.

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Identification of a Protein Subset of the Anthrax Spore Immunome in Humans Immunized with the Anthrax Vaccine Adsorbed Preparation

Infection and Immunity ◽

10.1128/iai.73.9.5685-5696.2005 ◽

2005 ◽

Vol 73 (9) ◽

pp. 5685-5696 ◽

Cited By ~ 28

Author(s):

Indira T. Kudva ◽

Robert W. Griffin ◽

Jeonifer M. Garren ◽

Stephen B. Calderwood ◽

Manohar John

Keyword(s):

Drug Targets ◽

Protective Antigen ◽

Hypothetical Protein ◽

The United States ◽

Surface Proteins ◽

Spore Surface ◽

Expression Library ◽

Anthrax Vaccine ◽

Anthrax Spore ◽

Anthrax Vaccines

ABSTRACTWe identified spore targets of Anthrax Vaccine Adsorbed (AVA)-induced immunity in humans by screening recombinant clones of a previously generated, limited genomicBacillus anthracisSterne (pXO1+, pXO2−) expression library of putative spore surface (spore-associated [SA]) proteins with pooled sera from human adults immunized with AVA (immune sera), the anthrax vaccine currently approved for use by humans in the United States. We identified 69 clones that reacted specifically with pooled immune sera but not with pooled sera obtained from the same individuals prior to immunization. Positive clones expressed proteins previously identified as localized on the anthrax spore surface, proteins highly expressed during spore germination, orthologs of proteins of diverse pathogens under investigation as drug targets, and orthologs of proteins contributing to the virulence of both gram-positive and gram-negative pathogens. Among the reactive clones identified by this immunological screen was one expressing a 15.2-kDa hypothetical protein encoded by a gene with no significant homology to sequences contained in databases. Further studies are required to define the subset of SA proteins identified in this study that contribute to the virulence of this pathogen. We hypothesize that optimal delivery of a subset of SA proteins identified by such studies to the immune system in combination with protective antigen (PA), the principal immunogen in AVA, might facilitate the development of defined, nonreactogenic, more-efficacious PA-based anthrax vaccines. Future studies might also facilitate the identification of SA proteins with potential to serve as targets for drug design, spore inactivation, or spore detection strategies.

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Rethinking Vaccine Development as an Integral Part of Preparedness in the European Health Union

European Journal of Risk Regulation ◽

10.1017/err.2020.95 ◽

2020 ◽

Vol 11 (4) ◽

pp. 821-830

Author(s):

Marco RIZZI

Keyword(s):

Public Health ◽

Risk Management ◽

Research And Development ◽

Paradigm Shift ◽

Vaccine Development ◽

Recent Past ◽

Vaccine Research ◽

Regulatory Frameworks ◽

European Health ◽

Epidemic Diseases

This opinion piece puts forward a critique of the policy and regulatory frameworks governing vaccines, understood as tools to confront pandemic and epidemic diseases (PEDs). Vaccines being the universally recognised prime method of prevention, immunisation campaigns and vaccine research and development (R&D) could reasonably be expected to feature prominently in any policy and/or strategic document addressing emerging health threats. Yet, vaccination occupies a relatively subsidiary role, with a prevalent focus on risk management mechanisms. This piece outlines the main characteristics of preparedness frameworks and looks at vaccine development in the course of PED outbreaks in the recent past, concluding that the COVID-19 pandemic calls for a paradigm shift in vaccine R&D, which should become integral to public health preparedness.

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Tracking HIV Post-Exposure Prophylaxis using Syndromic Surveillance in NYC Emergency Departments

Online Journal of Public Health Informatics ◽

10.5210/ojphi.v7i1.5755 ◽

2015 ◽

Vol 7 (1) ◽

Cited By ~ 2

Author(s):

Stephanie Ngai ◽

Zoe Edelstein ◽

Julie Myers ◽

Don Weiss

Keyword(s):

New York ◽

New York City ◽

Emergency Departments ◽

Syndromic Surveillance ◽

The United States ◽

Post Exposure Prophylaxis ◽

Syndromic Surveillance System ◽

Post Exposure ◽

Threefold Increase ◽

Exposure Prophylaxis

HIV post-exposure prophylaxis (PEP) prescriptions are not uniformly monitored in the United States. We developed a method to identify PEP-related visits in New York City emergency departments (EDs). Using ED data, we observed a threefold increase in PEP-related visits to NYC EDs from 2002-2013. 73% of PEP-related visits were among males, and 45% among adults ages 25-34 years. Incorporation of this method of PEP monitoring in the NYC syndromic surveillance system will be used to observe trends and inform HIV outreach efforts.

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Ethical Assessment of Post-Exposure Prophylaxis Guidelines in Sexual Assault Patients Suspected of Hepatitis B Viral Infection

The Journal of Healthcare Ethics & Administration ◽

10.22461/jhea.1.71631 ◽

2021 ◽

Vol 7 (3) ◽

pp. 29-37

Author(s):

Jimmy Mond ◽

Jeffrey Gruenglas

Keyword(s):

Sexual Assault ◽

Hepatitis B ◽

The United States ◽

Homeless Persons ◽

Treatment Modalities ◽

Post Exposure Prophylaxis ◽

Ethical Assessment ◽

Increased Risk ◽

The Disabled ◽

Exposure Prophylaxis

More than 400,000 sexual assaults are reported annually in the United States in females and males above the age of 12. Victims are likely to include members of vulnerable populations such as the disabled, homeless persons, and immigrants. Victims of such assaults are at heightened risk of contracting the Hepatitis B virus (HBV) from their assailant. Unfortunately, approximately two-thirds of people with chronic HBV are unaware of their own status, exposing for victims the risk viral transmission, disease-related cirrhosis, and hepatocellular carcinoma. Victims are also at increased risk for posttraumatic stress disorder (PTSD). Although immediate vaccination of the assaulted victim is recommended, protective levels of antibody are not present for fourteen days post vaccination. Complementary treatment with a Hepatitis B immune globulin (HBIG), however, may provide immediate protective serum concentrations. Prompt prophylactic therapeutic intervention may not only protect patients from risk of infection but may also prevent the effects of PTSD by providing victims with psychological and emotional benefit. Yet, existing Centers for Disease Control and Preventions (CDC) recommendations for suspected HBV infection in sexual assault patients recommend initiating immunoprophylaxis only in cases where the perpetrator’s HBsAg status is known, a guideline that perpetuates inequities and injustice for those equally subject to the harms of sexual assault. This paper presents an ethical assessment of prophylactic treatment for sexual assault patients suspected of HBV exposure. In the absence of equitable guidelines, we argue for the clinician’s duty to rescue sexually assaulted patients from future harm and to protect the public through mitigation of transmission using currently available and evidence-based treatment modalities. The paper concludes with an ethical foundation to advocate for modification of current guidelines in view of existing prophylactic regimens.

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Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

10.1101/2022.01.04.21268275 ◽

2022 ◽

Author(s):

Paul E Wischmeyer ◽

Helen Tang ◽

Yi Ren ◽

Lauren Bohannon ◽

Zeni E Ramirez ◽

...

Keyword(s):

Controlled Trial ◽

Lactobacillus Rhamnosus ◽

The United States ◽

Post Exposure Prophylaxis ◽

Event Analysis ◽

Double Blind ◽

Intention To Treat ◽

Tract Infections ◽

Exposure Prophylaxis ◽

Vaccine Availability

Background: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, supplemental strategies to mitigate the spread and severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to infections, including respiratory tract infections, may be reduced by probiotic interventions. Therefore, probiotics may be a low-risk, widely implementable modality to mitigate risk of COVID-19 disease, particularly in areas with low vaccine availability and/or uptake. Methods: We conducted a randomized, double-blind, placebo-controlled trial across the United States testing the probiotic Lactobacillus rhamnosus GG (LGG) as post-COVID-19-exposure prophylaxis. We enrolled individuals > 1 year of age with a household contact with a recent (≤ 7 days) diagnosis of COVID-19. Participants were randomized to receive daily LGG or placebo for 28 days. Stool was collected to evaluate the microbiome. The primary outcome was development of symptoms of illness compatible with COVID-19 within 28 days. Findings: We enrolled 182 COVID-19-exposed participants. Intention-to-treat analysis showed that participants randomized to LGG were less likely to develop symptoms versus those randomized to placebo (26.4% vs. 42.9%, p=0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank p=0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis was not significantly different between LGG (8.8%) and placebo (15.4%) (p=0.17). LGG was well-tolerated with no increased side effects versus placebo. Interpretation: These findings suggest that LGG probiotic may protect against the development of COVID-19 infection and symptoms when used as post-exposure prophylaxis within 7 days after exposure. Funding: This work was supported by a grant from the Duke Microbiome Center to A.D.S. and P.E.W. and private philanthropic donations to A.D.S. DSM/iHealth donated the LGG and placebo for the trial but had no role in its design, conduct, analysis, or writing. Trial registration: NCT04399252

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Cost effectiveness of rabies post exposure prophylaxis in the United States

Vaccine ◽

10.1016/j.vaccine.2008.05.048 ◽

2008 ◽

Vol 26 (33) ◽

pp. 4251-4255 ◽

Cited By ~ 20

Author(s):

Praveen Dhankhar ◽

Sagar A. Vaidya ◽

Daniel B. Fishbien ◽

Martin I. Meltzer

Keyword(s):

United States ◽

Cost Effectiveness ◽

The United States ◽

Post Exposure Prophylaxis ◽

Post Exposure ◽

Exposure Prophylaxis

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Structural Stigma Affects Access to Pre- and Post-exposure Prophylaxis and HIV Risk among Men Who Have Sex with Men (MSM) in the United States

AIDS Research and Human Retroviruses ◽

10.1089/aid.2014.5031.abstract ◽

2014 ◽

Vol 30 (S1) ◽

pp. A22-A23 ◽

Cited By ~ 7

Author(s):

Catherine Oldenburg ◽

Amaya Perez-Brumer ◽

Mark Hatzenbuehler ◽

Douglas Krakower ◽

David Novak ◽

...

Keyword(s):

United States ◽

Hiv Risk ◽

The United States ◽

Post Exposure Prophylaxis ◽

Post Exposure ◽

Sex With Men ◽

Exposure Prophylaxis

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688. Impact of Expanded Influenza Post-exposure Prophylaxis on Healthcare Worker Absenteeism at a Tertiary Care Center During the 2017–2018 Season

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.695 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S248-S248

Author(s):

Mireia Puig-Asensio ◽

Margaret Douglas ◽

Stephanie Holley ◽

Mary Beth Kukla ◽

Oluchi Abosi ◽

...

Keyword(s):

Sick Leave ◽

Healthcare Worker ◽

Care Center ◽

Tertiary Care ◽

Safety Net ◽

The United States ◽

Vaccination Status ◽

Post Exposure Prophylaxis ◽

Post Exposure ◽

Exposure Prophylaxis

Abstract Background A severe 2017–2018 influenza season was expected for the United States. We hypothesized that a surge in influenza cases paired with decreased vaccine effectiveness could increase healthcare worker (HCW) absenteeism. Because of a potential public health emergency during the 2017–2018 season, we offered oseltamivir post-exposure prophylaxis (PEP) to exposed HCWs regardless of vaccination status. We describe PEP uptake, cost, and impact on absenteeism at the University of Iowa Hospital and Clinics (UIHC). Methods UIHC serves as a referral and safety net health system for Eastern Iowa. Influenza seasons were defined as the period between Week 40 from 1 year to Week 13 of the following year. During the 2016–2017 season, PEP (75 mg/day for 7 days) was offered free of charge to unvaccinated exposed HCWs. Exposure was defined as proximity within 3 ft of a confirmed influenza-infected person for ≥10 minutes without mask protection, or direct contact with respiratory secretions. During the 2017–2018 season, PEP was expanded to all exposed HCWs regardless of vaccination status. We reviewed surveillance, employee health, pharmacy, and human resources records for the 2016–2017 and 2017–2018 seasons. We defined PEP uptake as prescriptions picked up/all referrals and absenteeism rate as sick-leave requests/scheduled hours. Results During the 2016–2017 and 2017–2018 seasons, we detected 373 and 427 confirmed influenza cases among patients at UIHC. HCW vaccination rates were similar: 89.7% and 90.9%. PEP was recommended in 49 exposures during 2016–2017 and 280 exposures during 2017–2018. A total of 22 (44.9%) and 133 (47.5%) HCWs picked up oseltamivir from the pharmacy during the 2016–2017 and 2017–2018 seasons. The estimated cost of oseltamivir was $1,791 and $10,828, respectively. Overall, 6,187 sick-leave requests (median = 12 hours, absenteeism rate = 3.2%), and 6,174 sick-leave requests (median = 12 hours, absenteeism rate = 3.4%) were reported during the 2016–2017 and 2017–2018 seasons. Conclusion Influenza case counts mildly increased from the 2016–2017 to the 2017–2018 season. Expanding PEP to all exposed HCWs, regardless of vaccination status, had moderate uptake and was costly. Absenteeism rates remained similar during both seasons. Disclosures All authors: No reported disclosures.

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Findings from the initial Stepwise Approach to Rabies Elimination (SARE) Assessment in China, 2019

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0009274 ◽

2021 ◽

Vol 15 (3) ◽

pp. e0009274

Author(s):

Qiulan Chen ◽

Xiaoyue Ma ◽

Jeanette J. Rainey ◽

Yu Li ◽

Di Mu ◽

...

Keyword(s):

Disease Control ◽

Vaccination Coverage ◽

Assessment Tool ◽

Animal Health ◽

The United States ◽

Human Rabies ◽

Post Exposure Prophylaxis ◽

Stepwise Approach ◽

Control And Prevention ◽

Exposure Prophylaxis

In 2015, China and other member states of the United Nations adopted the goal of eliminating dog-mediated rabies by 2030. China has made substantial progress in reducing dog-mediated human rabies since peaking with more than 3,300 reported cases in 2007. To further improve coordination and planning, the Chinese Center for Disease Control and Prevention, in collaboration with the United States Centers for Disease Control and Prevention, conducted a Stepwise Approach towards Rabies Elimination (SARE) assessment in March 2019. Assessment goals included outlining progress and identifying activities critical for eliminating dog-mediated rabies. Participants representing national, provincial and local human and animal health sectors in China used the SARE assessment tool to answer 115 questions about the current dog-mediated rabies control and prevention programs in China. The established surveillance system for human rabies cases and availability of post-exposure prophylaxis were identified as strengths. Low dog vaccination coverage and limited laboratory confirmation of rabid dogs were identified gaps, resulting in an overall score of 1.5 on a scale of 0 to 5. Participants outlined steps to increase cross-sectoral information sharing, improve surveillance for dog rabies, increase dog vaccination coverage, and increase laboratory capacity to diagnose rabies at the provincial level. All assessment participants committed to strengthening cross-sector collaboration using a One Health approach to achieve dog-mediated human rabies elimination by 2030.

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