Vaccine Stockpile Research Articles

Co‐benefits and ‘no regrets’ benefits of influenza pandemic planning

To the editor: The emergence of the influenza A (H1N1) pandemic strain in 2009 and its subsequent spread has stimulated national and international interest in pandemic influenza control. It is likely to also be stimulating further revisions of pandemic plans around the world, especially given the possibility of on‐going waves. 1 Such pandemic planning can involve sunk costs that might never be realised e.g., antiviral and vaccine stockpiles. However, there are many other potential collateral benefits from pandemic planning and preparations that can be realised regardless of a future pandemic occurring. We briefly describe some of these in this letter.

Preservation of the Immunogenicity of Dry-powder Influenza H5N1 Whole Inactivated Virus Vaccine at Elevated Storage Temperatures

Stockpiling of pre-pandemic influenza vaccines guarantees immediate vaccine availability to counteract an emerging pandemic. Generally, influenza vaccines need to be stored and handled refrigerated to prevent thermal degradation of the antigenic component. Requirement of a cold-chain, however, complicates stockpiling and the logistics of vaccine distribution. We, therefore, investigated the effect of elevated storage temperatures on the immunogenicity of a pre-pandemic influenza A H5N1 whole inactivated virus vaccine. Either suspended in liquid or kept as a freeze-dried powder, vaccines could be stored for 1 year at ambient temperature (20°C) with minimal loss of immunogenicity in mice. Elevation of the storage temperature to 40°C, however, resulted in a significant loss of immunogenic potency within 3 months if vaccines were stored in liquid suspension. In sharp contrast, freeze-dried powder formulations were stable at 40°C for at least 3 months. The presence of inulin or trehalose sugar excipients during freeze-drying of the vaccine proved to be critical to maintain its immunogenic potency during storage, and to preserve the characteristic Th1-type response to whole inactivated virus vaccine. These results indicate that whole inactivated virus vaccines may be stored and handled at room temperature in moderate climate zones for over a year with minimal decline and, if converted to dry-powder, even in hot climate zones for at least 3 months. The increased stability of dry-powder vaccine at 40°C may also point to an extended shelf-life when stored at 4°C. Use of the more stable dry-powder formulation could simplify stockpiling and thereby facilitating successful pandemic intervention.

A multi-attribute approach for setting pediatric vaccine stockpile levels

Routine immunization is the most effective public health strategy to prevent the occurrence and spread of infectious diseases. An important factor impacting such effectiveness is the availability of a stable vaccine supply. Vaccine supply interruptions are likely and can prevent children from receiving a full course of vaccinations and hence, increase the risk of disease outbreaks. In the United States, public health officials have established the Pediatric Vaccine Stockpile Program (PVSP) as the best strategy to mitigate the impact of vaccine supply interruptions. The PVSP aims to maintain a six-month national supply of routinely administered pediatric vaccines. When deciding how many vaccine doses to order for the next fiscal year, public health decision-makers must not only minimize the impact of potential vaccine shortages, but also, maintain or increase vaccine coverage rates while minimizing costs. This paper uses the relative importance of each pediatric vaccine to define a multi-attribute utility function that models the conflicting interests of PVSP public health decision-makers when ordering vaccines for the next fiscal year. The aim of the resulting framework is to assist decision-makers in managing the PVSP. As an illustration, this paper explores the implications of optimizing a proposed expected utility function under budget constraints for hypothetical (albeit likely) vaccine supply scenarios, and the potential behavior of public health decision-makers.

Economic Analysis of Pandemic Influenza Vaccination Strategies in Singapore

BackgroundAll influenza pandemic plans advocate pandemic vaccination. However, few studies have evaluated the cost-effectiveness of different vaccination strategies. This paper compares the economic outcomes of vaccination compared with treatment with antiviral agents alone, in Singapore.MethodologyWe analyzed the economic outcomes of pandemic vaccination (immediate vaccination and vaccine stockpiling) compared with treatment-only in Singapore using a decision-based model to perform cost-benefit and cost-effectiveness analyses. We also explored the annual insurance premium (willingness to pay) depending on the perceived risk of the next pandemic occurring.Principal FindingsThe treatment-only strategy resulted in 690 deaths, 13,950 hospitalization days, and economic cost of USD$497 million. For immediate vaccination, at vaccine effectiveness of >55%, vaccination was cost-beneficial over treatment-only. Vaccine stockpiling is not cost-effective in most scenarios even with 100% vaccine effectiveness. The annual insurance premium was highest with immediate vaccination, and was lower with increased duration to the next pandemic. The premium was also higher with higher vaccine effectiveness, attack rates, and case-fatality rates. Stockpiling with case-fatality rates of 0.4–0.6% would be cost-beneficial if vaccine effectiveness was >80%; while at case-fatality of >5% stockpiling would be cost-beneficial even if vaccine effectiveness was 20%. High-risk sub-groups warrant higher premiums than low-risk sub-groups.ConclusionsThe actual pandemic vaccine effectiveness and lead time is unknown. Vaccine strategy should be based on perception of severity. Immediate vaccination is most cost-effective, but requires vaccines to be available when required. Vaccine stockpiling as insurance against worst-case scenarios is also cost-effective. Research and development is therefore critical to develop and stockpile cheap, readily available effective vaccines.

IMVAMUNE®: modified vaccinia Ankara strain as an attenuated smallpox vaccine

Smallpox vaccines based on replicating vaccinia virus are known to elicit rare yet serious adverse events, particularly in human populations with immune deficiency, atopic dermatitis and at the extremes of age. A vaccine that induces protective immune responses equivalent to first-generation smallpox vaccines while reducing the risk for severe adverse events is critical for a national stockpile of smallpox vaccines. Modified vaccinia Ankara (MVA) has been proposed as an immediate solution for vaccination of high-risk individuals. Bavarian Nordic’s vaccine MVA-BN® (IMVAMUNE®) is a MVA strain that is replication incompetent in mammalian cell lines. IMVAMUNE has been administered to more than 1900 human subjects to date, including high-risk populations (e.g., people diagnosed with atopic dermatitis or infected with HIV) in which standard replicating vaccines are contraindicated. We review the Phase I clinical trial safety profile and immune responses and compare them with other smallpox vaccines, including ACAM2000™ and Dryvax®.

Yellow fever vaccine: past, present and future

Background: Yellow fever is a re-emerging infectious disease, as vector control and routine immunisation have dwindled in endemic areas in the last few decades. There is a constant threat of outbreaks in the large susceptible non-immune population of the megacities in tropical countries with an ongoing virus life cycle in the rainforests. For this population and for travellers to endemic areas, vaccination is the only effective protective measure against the disease and the spread of the virus. Objective/methods: We discuss the history of yellow fever vaccine development, and focus on practical aspects of vaccine safety, contraindications for vaccination, and future vaccine developments. Results/conclusions: Vaccination with the live attenuated yellow fever-17D vaccine (YF-17D) induces low-grade viraemia in half of the vaccinees and elicits protective neutralising antibody levels in 99%. Reports of serious adverse events in the elderly and immunocompromised, and the inability to produce large quantities of yellow fever vaccine at short notice in combination with limited vaccine stockpiles highlight the need for further study of this highly effective and safe vaccine.

Predominant role of bacterial pneumonia as a cause of death in pandemic influenza: implications for pandemic influenza preparedness.

Despite the availability of published data on 4 pandemics that have occurred over the past 120 years, there is little modern information on the causes of death associated with influenza pandemics. We examined relevant information from the most recent influenza pandemic that occurred during the era prior to the use of antibiotics, the 1918-1919 "Spanish flu" pandemic. We examined lung tissue sections obtained during 58 autopsies and reviewed pathologic and bacteriologic data from 109 published autopsy series that described 8398 individual autopsy investigations. The postmortem samples we examined from people who died of influenza during 1918-1919 uniformly exhibited severe changes indicative of bacterial pneumonia. Bacteriologic and histopathologic results from published autopsy series clearly and consistently implicated secondary bacterial pneumonia caused by common upper respiratory-tract bacteria in most influenza fatalities. The majority of deaths in the 1918-1919 influenza pandemic likely resulted directly from secondary bacterial pneumonia caused by common upper respiratory-tract bacteria. Less substantial data from the subsequent 1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza vaccines and antiviral drugs). Prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia, as well as stockpiling of antibiotics and bacterial vaccines, should also be high priorities for pandemic planning.

Stockpiling prepandemic influenza vaccines: a new cornerstone of pandemic preparedness plans

The history of pandemic influenza, along with the evolving epizootic of the highly pathogenic avian influenza A (H5N1) virus and the severity of associated human infections, serve as a warning to the world of the threat of another influenza pandemic. Conservative estimates suggest that up to 350 million people could die and many more would be affected, causing disruption to health-care systems, society, and the world's economy. WHO has encouraged countries to prepare in advance by developing influenza pandemic preparedness plans that involve public-health and pharmaceutical interventions. Vaccination is a cornerstone of these plans; however, a pandemic vaccine cannot be manufactured in advance because the next pandemic virus cannot be predicted. The concepts of vaccine stockpiling and prepandemic vaccination have thus become attractive. Human H5N1 vaccines are currently available and can induce heterotypic immunity. WHO and governments should give urgent consideration to the use of these vaccines for the priming of individuals or communities who would be at greatest risk of infection if an H5N1 influenza pandemic were to emerge.

A large-scale simulation model of pandemic influenza outbreaks for development of dynamic mitigation strategies

Limited stockpiles of vaccine and antiviral drugs and other resources pose a formidable healthcare delivery challenge for an impending human-to-human transmittable influenza pandemic. The existing preparedness plans by the Center for Disease Control and Health and Human Services strongly underscore the need for efficient mitigation strategies. Such a strategy entails decisions for early response, vaccination, prophylaxis, hospitalization and quarantine enforcement. This paper presents a large-scale simulation model that mimics stochastic propagation of an influenza pandemic controlled by mitigation strategies. The impact of a pandemic is assessed via measures including total numbers of infected, dead, denied hospital admission and denied vaccine/antiviral drugs, and also through an aggregate cost measure incorporating healthcare cost and lost wages. The model considers numerous demographic and community features, daily human activities, vaccination, prophylaxis, hospitalization, social distancing, and hourly accounting of infection spread. The simulation model can serve as the foundation for developing dynamic mitigation strategies. The simulation model is tested on a hypothetical community with over 1100 000 people. A designed experiment is conducted to examine the statistical significance of a number of model parameters. The experimental outcomes can be used in developing guidelines for strategic use of limited resources by healthcare decision makers. Finally, a Markov decision process model and its simulation-based reinforcement learning framework for developing mitigation strategies are presented. The simulation-based framework is quite comprehensive and general, and can be particularized to other types of infectious disease outbreaks.

Clinical and immune response to undiluted and diluted smallpox vaccine.

To assess clinical reactions, immune responses and adverse events to undiluted, three- and sixfold diluted Lister strain vaccine stockpiled in Switzerland. A prospective, triple-blinded, randomised, parallel group clinical trial was performed. From 2001 to 2007 104 persons with an indication for vaccinia vaccination were recruited. They had a median age of 33 years (range 18-65), 56 (53.8%) were re-vaccinees and 48 (46.2%) primary vaccinees. There was no statistically significant variation in the proportion of revaccinees between diluted and undiluted vaccine groups (75% vs 51%, p = 0.118). With an overall clinical take rate (major reaction) of 97.1% the majority of the vaccinia-naïve participants exhibited an at least fourfold increase of neutralising antibody titres (32/38, 84.2%) post-vaccination. Interestingly this proportion was lower among re-vaccinees (29/46, 63.0%, p = 0.048). No significant difference was observed in the take rate or at least fourfold seroconversion rate between the threefold and sixfold diluted vaccine doses. Adverse events were reported by 98 (94.2%) participants, not accounting for itching at the vaccination site. Subjects requiring immunisation were successfully (re-) vaccinated with undiluted as well as with three- or sixfold diluted vaccinia vaccine. Our findings complement previous studies with respect to the clinical take rate and immune response. The rate of adverse events was substantial but not unexpected and no severe adverse events occurred. In conclusion, the existing smallpox vaccine stockpile might be expanded by administering three- or sixfold diluted vaccine doses combined with a careful pre-vaccination screening and extensive instructions to vaccinees.

Clinical and immune response to undiluted and diluted smallpox vaccine.

To assess clinical reactions, immune responses and adverse events to undiluted, three- and sixfold diluted Lister strain vaccine stockpiled in Switzerland. A prospective, triple-blinded, randomised, parallel group clinical trial was performed. From 2001 to 2007 104 persons with an indication for vaccinia vaccination were recruited. They had a median age of 33 years (range 18-65), 56 (53.8%) were re-vaccinees and 48 (46.2%) primary vaccinees. There was no statistically significant variation in the proportion of revaccinees between diluted and undiluted vaccine groups (75% vs 51%, p = 0.118). With an overall clinical take rate (major reaction) of 97.1% the majority of the vaccinia-naïve participants exhibited an at least fourfold increase of neutralising antibody titres (32/38, 84.2%) post-vaccination. Interestingly this proportion was lower among re-vaccinees (29/46, 63.0%, p = 0.048). No significant difference was observed in the take rate or at least fourfold seroconversion rate between the threefold and sixfold diluted vaccine doses. Adverse events were reported by 98 (94.2%) participants, not accounting for itching at the vaccination site. Subjects requiring immunisation were successfully (re-) vaccinated with undiluted as well as with three- or sixfold diluted vaccinia vaccine. Our findings complement previous studies with respect to the clinical take rate and immune response. The rate of adverse events was substantial but not unexpected and no severe adverse events occurred. In conclusion, the existing smallpox vaccine stockpile might be expanded by administering three- or sixfold diluted vaccine doses combined with a careful pre-vaccination screening and extensive instructions to vaccinees.

Effective, Robust Design of Community Mitigation for Pandemic Influenza: A Systematic Examination of Proposed US Guidance

BackgroundThe US government proposes pandemic influenza mitigation guidance that includes isolation and antiviral treatment of ill persons, voluntary household member quarantine and antiviral prophylaxis, social distancing of individuals, school closure, reduction of contacts at work, and prioritized vaccination. Is this the best strategy combination? Is choice of this strategy robust to pandemic uncertainties? What are critical enablers of community resilience?Methods and FindingsWe systematically simulate a broad range of pandemic scenarios and mitigation strategies using a networked, agent-based model of a community of explicit, multiply-overlapping social contact networks. We evaluate illness and societal burden for alterations in social networks, illness parameters, or intervention implementation. For a 1918-like pandemic, the best strategy minimizes illness to <1% of the population and combines network-based (e.g. school closure, social distancing of all with adults' contacts at work reduced), and case-based measures (e.g. antiviral treatment of the ill and prophylaxis of household members). We find choice of this best strategy robust to removal of enhanced transmission by the young, additional complexity in contact networks, and altered influenza natural history including extended viral shedding. Administration of age-group or randomly targeted 50% effective pre-pandemic vaccine with 7% population coverage (current US H5N1 vaccine stockpile) had minimal effect on outcomes. In order, mitigation success depends on rapid strategy implementation, high compliance, regional mitigation, and rigorous rescinding criteria; these are the critical enablers for community resilience.ConclusionsSystematic evaluation of feasible, recommended pandemic influenza interventions generally confirms the US community mitigation guidance yields best strategy choices for pandemic planning that are robust to a wide range of uncertainty. The best strategy combines network- and case-based interventions; network-based interventions are paramount. Because strategies must be applied rapidly, regionally, and stringently for greatest benefit, preparation and public education is required for long-lasting, high community compliance during a pandemic.

Ready for avian flu?

Committing to a vaccine stockpile is just the beginning. Tadataka Yamada, Alice Dautry and Mark Walport offer a roadmap for heading off a global avian influenza catastrophe. The 'official' influenza vaccine failed this year. Each year the World Health Organization selects strains for the vaccine based on epidemiological data. Most of the time it works, but what can be done to prevent future failures? Steven Salzberg thinks the answer lies in better tracking of virus mutations. This means that some research groups need to change their ways. Instead of guarding their data, the priority should be the rapid dissemination of genome sequence data on all isolates — human and avian. More transparency is one of the recommendations made by Yamada et al. in a checklist on how we should prepare for the next influenza pandemic. Other suggestions include stockpiling standard (inter-pandemic) flu vaccine, a special pricing model for poor countries, and improved surveillance mechanisms. For more on this week's Commentaries, visit the podcast page.

Donor leverage: towards more equitable access to essential medicines?

In early 2007, the Indonesian government decided to withhold its samples of the avian influenza (‘bird flu’) virus from WHO's collaborating centres, pending a new global mechanism for virus sharing which would provide better terms for developing countries. The 60th World Health Assembly held in May 2007 subsequently resolved to establish an international stockpile of avian influenza vaccines, and to formulate mechanisms for equitable access to these vaccines. The article asks whether there are there analogous opportunities for study volunteers or donors of biological materials to exercise corresponding leverage to advance health equity.

Optimizing the Dose of Pre-Pandemic Influenza Vaccines to Reduce the Infection Attack Rate

BackgroundThe recent spread of avian influenza in wild birds and poultry may be a precursor to the emergence of a 1918-like human pandemic. Therefore, stockpiles of human pre-pandemic vaccine (targeted at avian strains) are being considered. For many countries, the principal constraint for these vaccine stockpiles will be the total mass of antigen maintained. We tested the hypothesis that lower individual doses (i.e., less than the recommended dose for maximum protection) may provide substantial extra community-level benefits because they would permit wider vaccine coverage for a given total size of antigen stockpile.Methods and FindingsWe used a mathematical model to predict infection attack rates under different policies. The model incorporated both an individual's response to vaccination at different doses and the process of person-to-person transmission of pandemic influenza. We found that substantial reductions in the attack rate are likely if vaccines are given to more people at lower doses. These results are applicable to all three vaccine candidates for which data are available. As a guide to the magnitude of the effect, we simulated epidemics based on historical studies of immunogenicity. For example, for one of the vaccines for which data are available, the attack rate would drop from 67.6% to 58.7% if 160 out of the total US population of 300 million were given an optimal dose rather than 20 out of 300 million given the maximally protective dose (as promulgated in the US National Pandemic Preparedness Plan). Our results are conservative with respect to a number of alternative assumptions about the precise nature of vaccine protection. We also considered a model variant that includes a single high-risk subgroup representing children. For smaller stockpile sizes that allow vaccine to be offered only to the high-risk group at the optimal dose, the predicted benefits of using the homogenous model formed a lower bound in the presence of a risk group, even when the high-risk group was twice as infective and twice as susceptible.ConclusionsIn addition to individual-level protection (i.e., vaccine efficacy), the population-level implications of pre-pandemic vaccine programs should be considered when deciding on stockpile size and dose. Our results suggest that a lower vaccine dose may be justified in order to increase population coverage, thereby reducing the infection attack rate overall.

WHO recommendations to establish a stockpile of vaccine against H5N1 influenza virus have received support from vaccine manufacturers,

WHO recommendations to establish a stockpile of vaccine against H5N1 influenza virus have received support from vaccine manufacturers,

Assessing Influenza Vaccine Utilization in Physician Offices Serving Adult Patients

Influenza vaccination among US adults has plateaued at suboptimal levels. Severe delays and shortages of influenza vaccine prompted revised guidances to prioritize vaccine first to persons at greatest risk for serious influenza complications and to create vaccine stockpiles. (1) Pilot an assessment of influenza vaccine use in a large sample of physician offices with adult patients. (2) Apply the method to assess vaccine receipt by age and risk groups. Influenza vaccination and risk status for the 2000-2001 season were obtained from record review conducted in November 2001 to April 2002 for adult patients in a sample of physicians' offices in eight states. Participating physicians also completed a questionnaire. The assessment method was feasible to implement. One hundred eighteen physicians participated. They administered more than 83 percent of doses to prioritized groups in October and November compared with 74 percent of doses during the entire season. Office-based vaccination coverage was less than 40 percent in all age and risk groups. More than 50 percent of participating physicians reported unused doses. Office-based assessments of vaccine utilization can be a valuable evaluation tool. Vaccine distribution was consistent with recommendations to target early vaccination to priority groups. Results highlight the difficulty distributing vaccine late in the season and the need for strategies to improve vaccination coverage, particularly when vaccine supply is inadequate.

Reducing the Dose of Smallpox Vaccine Reduces Vaccine‐Associated Morbidity without Reducing Vaccination Success Rates or Immune Responses

When the decision was made to prepare for a deliberate release of smallpox, the United States had approximately 15 million doses of Wyeth Dryvax vaccine, which was known to induce significant morbidity when used undiluted; Sanofi Pasteur, Inc., later identified approximately 85 million additional doses in storage. Eleven vaccine-dose groups, each with 30 vaccinia-naive subjects, were given diluted Dryvax vaccine or 1 of 2 lots of Sanofi Pasteur smallpox vaccine and were evaluated for vaccination success rates, morbidity, and immune responses. Estimated doses of 10(6.6)-10(8.2) pfu of virus/mL induced major reactions (or "takes") in 93%-100% of subjects in each dose group. No differences in vaccination take rates, lesion size, erythema, and induration or in serum neutralizing-antibody response were detected between the groups. However, systemic reactogenicity and missed activities were significantly lower for the vaccine groups given doses of 10(6.6)-10(7.2) pfu/mL than for those given doses of 10(7.6)-10(8.2) pfu/mL. These findings support the use of a higher dilution of Wyeth Dryvax vaccine and Sanofi Pasteur smallpox vaccine, given that the resulting morbidity should be significantly lower without loss of vaccine effectiveness. A plan for use of higher dilutions would create an enormous stockpile of vaccine.

Will the Post 9/11 World Be a Post-Tort World?

This essay looks at the impact of 9/11 on provisions for civil recourse by victims of harm. The short answer to the title question is: NO. But tort law will continue to be eroded by attrition, by lopping off remedies - especially by limiting damages and expanding immunities - unless we are able to grab hold of the public's conscience and consciousness to bring home the point that liability in tort is not some form of punishment, erratically inflicted. We discuss and analyze the legislative responses that followed: * the September 11 Victims Compensation Fund * establishment of the World Trade Center Captive Insurance Company to provide defense and excess liability insurance of $1 billion to the City of New York and its contractors. * the smallpox vaccination campaign and the liability limitations and modest compensation scheme of the Smallpox Emergency Personnel Protection Act of 2003. * the adoption of the government contractor defense for suppliers of qualified anti-terrorism technology to the newly created Department of Homeland Security in the SAFETY Act of 2004. * the BioShield Act of 2004 which established a strategic national stockpile of drugs, vaccines and other biological products, medical devices, and other supplies for use in the event of bioterrorist attack or public health emergency. * The Public Readiness and Emergency Preparedness Act of 2005,(PREPA) which declares targeted liability protections for pandemic and epidemic products and security countermeasures. * S. 2291, a bill introduced in 2006 by the Democratic leadership, would repeal the PREPA and create a defense in a narrow class of medical products for which use is permitted without completing the usual regulatory vetting, due to their importance in a threatened emergency. We discuss the ATSSSA, reviewing the strengths and weaknesses of the tort claims of those who were injured and died on 9/11. Next reviewed are the WTC respiratory injury occupational disease tort claims, their necessity and justice, examining their vulnerability in light of the immunity and lack of duty defenses raised. The claims affirm the importance and vigor of the tort remedy. The other post 9/11 liability-limiting legislative measures are discussed. They provide broad protection for many classes of actors and sellers, including administrators and producers of vaccines. A survey of the historic experience with the Swine Flu vaccine campaign of 1976 shows the centrality of familiar tort liability principles of responsibility. In the Swine Flu vaccination the government stood in the shoes of vaccine manufacturers. The United States admitted strict liability in tort for some vaccine complications (such as confirmed paralytic Guillain Barre Syndrome), and fought others. And under the Federal Tort Claims Act the United States defended its own hard sell of the Swine Flu vaccine. Liability was imposed on the United States itself for the Centers for Disease Control's failure to adequately inform citizens of vaccine risks. The British Hepatitis C-contaminated blood cases are discussed as another important instance of government agency liability. There the National Blood Authority was held accountable as collector and distributor of blood products for its tardy implementation of an effective test for viral contamination. First presented as the 2006 Raynes McCarty Distinguished Health Law Lecture, Widener Law School, October 11, 2006

An analysis of the pediatric vaccine supply shortage problem

In 2002, several factors resulted in pediatric vaccine manufacturers not being able to produce a sufficient number of vaccines to vaccinate all the children in the United States according to the Recommended Childhood Immunization Schedule. The resulting vaccine supply shortage resulted in thousands of children not being fully immunized according to this schedule, and hence, created an unnecessary risk for epidemic outbreaks of several childhood diseases. The Centers for Disease Control and Prevention responded to this crisis by using pediatric vaccine stockpiles to mitigate the impact of future shortages. This paper presents a stochastic model that captures the vaccine supply during production interruptions. This model is used to assess the impact of pediatric vaccine stockpile levels on vaccination coverage rates, by considering the probability that all children can be immunized according to the Recommended Childhood Immunization Schedule over a given time period and the expected minimum vaccine supply. The model is also used to assess the proposed pediatric vaccine stockpile levels recommended by the United States Department of Health and Human Services. The results of this analysis suggest that the proposed vaccine stockpile levels are adequate to meet future vaccine production interruptions, provided that such production interruptions do not last more than six months (which is not surprising, given that is the time period for which they were designed). However, given that recent vaccine production interruptions have lasted (on average) for over one year, the proposed vaccine stockpile levels are insufficient to meet the nation's pediatric immunization needs during such time periods, which in turn could lead to localized and/or widespread disease outbreaks. Moreover, a moderate investment in higher vaccine stockpile levels would lead to a significantly reduced risk of such events.