Chemistry,manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers

With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization’s (WHO’s) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic.Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China.The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements.Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs.     

Stakeholders’ perceptions of 10 years of the Global Action Plan for Influenza Vaccines (GAP) – Results from a survey

Ten years after the launch of the Global Action Plan for Influenza Vaccines (GAP), the World Health Organization (WHO) surveyed stakeholders to understand their perceptions of what the programme had achieved. This article provides a summary of the findings; the full report will be available on-line on the GAP website in November 2016 (http://www.who.int/influenza_vaccines_plan/en/). Seventy-seven responses were received from stakeholders including medical doctors, national influenza center officials, country immunization programme teams, surveillance and disease centers, policy-makers, researchers, vaccine manufacturers, and non-governmental organizations from 28 countries, representing all six WHO regions.Respondents cited GAP’s biggest successes as capacity building in developing countries; raising international awareness of global needs in the event of a pandemic; and collaborative alignment of influenza stakeholders. The most commonly reported challenges were the limited progress in development of a broadly protective or universal vaccine and the perceived absence of a major increase in seasonal demand. These findings aligned with the perception that less global progress had been made under the third GAP objective, focused on research and development of better vaccines, than on increasing seasonal vaccine use (objective 1) and pandemic vaccine production capacity (objective 2). Respondents explained what they saw as the major challenges to development of better vaccines, including to development of a universal influenza vaccine. The majority of respondents agreed that the goal chosen at the GAP II consultation is still relevant. Results highlighted the importance of promoting research and development of better vaccines, both for facilitating uptake of seasonal vaccines and for ensuring timely vaccine availability in the event of a pandemic. As the GAP concludes its mandate this year, these findings will contribute to discussions on the impact of programme closure and how to address the key issues facing influenza stakeholders thereafter.     

Challenges and successes for the grantees and the Technical Advisory Group of WHO’s influenza vaccine technology transfer initiative

One of the aims of the WHO Global Action Plan for Influenza Vaccines (GAP) was to transfer influenza vaccine production technology to interested manufacturers and governments in developing countries, to enable greater influenza vaccine manufacturing capacity against any pandemic threat or pandemic. For this objective, the GAP was supported by an independent Technical Advisory Group (TAG) to assist WHO to select vaccine manufacturing proposals for funding and to provide programmatic support for successful grantees. While there were many challenges, for both the TAG and grantees, there were also notable successes with an additional capacity of 338–600 million pandemic vaccine doses being made possible by the programme between 2007 and 2015, and a potential capacity of more than 600 million by 2016/17 with up to one billion doses expected by 2018/19. Seasonal vaccine production was also developed in 4 countries with another 4–5 countries expected to be producing seasonal vaccine by 2018/19. The relatively small WHO investments – in time and funding – made in these companies to develop their own influenza vaccine production facilities have had quite dramatic results.     

Technology transfer of an oil-in-water vaccine-adjuvant for strengthening pandemic influenza preparedness in Indonesia

With the current enzootic circulation of highly pathogenic avian influenza viruses, the ability to increase global pandemic influenza vaccine production capacity is of paramount importance. This has been highlighted by, and is one of the main pillars of, the WHO Global Action Plan for Influenza Vaccines (GAP). Such capacity expansion is especially relevant in developing countries. The Vaccine Formulation Laboratory at University of Lausanne is engaged in the technology transfer of an antigen-sparing oil-in-water adjuvant in order to empower developing countries vaccine manufacturers to increase pandemic influenza vaccine capacity. In a one-year project funded by United States Department of Health and Human Services, the Vaccine Formulation Laboratory transferred the process know-how and associated equipment for the pilot-scale manufacturing of an oil-in-water adjuvant to Bio Farma, Indonesia's state-owned vaccine manufacturer, for subsequent formulation with H5N1 pandemic influenza vaccines. This paper describes the experience acquired and lessons learnt from this technology transfer project.     

Global production capacity of seasonal influenza vaccine in 2011

The effectiveness of vaccines to mitigate the impact of annual seasonal influenza epidemics and influenza pandemics has been well documented. However, the steady increase in global capacity to produce annual seasonal influenza vaccine has not been matched with increased demand, and thus actual vaccine production. Currently, without a significant increase in demand for seasonal influenza vaccine, global capacity will be far from able to meet even the essential needs for a monovalent vaccine in the event of a severe influenza pandemic. Global commitment to the development of influenza vaccine production capacity was renewed at a consultation leading to the Second Global Action Plan on Influenza Vaccines (GAP) in July 2011. To monitor progress on the GAP, the World Health Organization has carried out periodic surveys of influenza vaccine manufacturers. This latest survey compares current maximum global capacity and actual production of seasonal influenza vaccine in 2011 with data from surveys carried out in 2009 and 2010; analyses global influenza production capacity in the context of sustainability; and discusses options to increase demand, based on strong evidence of public health benefit.     

A decade of adaptation: Regulatory contributions of the World Health Organization to the Global Action Plan for Influenza Vaccines (2006–2016)

The Global Action Plan (GAP) for Influenza Vaccines is a decade-long initiative that brings together a diverse range of stakeholders to work towards reducing anticipated global shortage of influenza vaccines and ensuring more equitable access to vaccines during the next influenza pandemic. Since its inception in 2006, significant progress has been made towards all the main objectives of GAP, namely: (1) an increase in seasonal vaccine use, (2) an increase in vaccine production, and (3) progress in research and development of more effective vaccines. The Technology Transfer Initiative (TTI), conceived and managed by WHO under the GAP, contributed to increasing regional influenza vaccine production capacity. This was achieved by facilitating technology transfer in 14 low- and middle-income countries, through grants to manufacturers to establish or strengthen influenza vaccine production capacity and support to their national regulatory authorities. Five of the countries subsequently licensed locally produced influenza vaccines; two pandemic and three seasonal vaccines received WHO prequalification. The success of GAP can be largely attributed to the regulatory support provided by WHO to both manufacturers and regulators. This support had two components: (1) direct regulatory support to GAP/TTI, and (2) support to GAP-related WHO programmes, such as the Pandemic Influenza Vaccine Deployment Initiative in 2010 and the Pandemic Influenza Preparedness Framework since 2013, especially in non-vaccine-producing countries. Temporary adaptation of the assessment process for influenza vaccines in the WHO Vaccine Prequalification Programme to the A(H1N1) pandemic situation in 2009 was instrumental to the success of the WHO Pandemic Influenza Vaccine Deployment Initiative in its attempt to meet the demand for pandemic vaccines in countries that received donated vaccines.     

United States of America Department of Health and Human Services support for advancing influenza vaccine manufacturing in the developing world

Since 2005, the Government of the United States of America has provided more than US$ 50 million to advance influenza vaccine development in low-resourced countries. This programme has provided a unique opportunity for the US Government to develop a comprehensive view of, and to understand better the challenges and future needs for influenza vaccines in the developing world. The funding for this programme has been primarily through a cooperative agreement with the World Health Organization (WHO) to support directly its capacity-building grants to government-owned or -supported vaccine manufacturers in developing countries. A second cooperative agreement with the Program for Appropriate Technologies in Health (PATH) was initiated to accelerate the completion of a current Good Manufacturing Practice cGMP production facility, along with supporting facilities to obtain a reliable source of eggs, and to conduct clinical trials of influenza vaccine manufactured in Vietnam. This mechanism of utilizing cooperative agreements to support capacity-building for vaccine development in low-resourced settings has been novel and unique and has yielded fruitful returns on minimal investment. The information derived from this programme helps to clarify not only the development challenges for influenza vaccines and how the United States may assist in meeting those challenges, but also other vaccine development issues common to manufacturers in developing countries. While building the initial capacity to produce influenza vaccines can be a straightforward exercise, the sustainability of the enterprise and expansion of subsequent markets will be the key to future usefulness. There is hope for expansion of the global influenza vaccine market. Ongoing burden of disease studies are elucidating the impact of influenza infections, particularly in children, and more countries will take note and respond accordingly, since respiratory diseases are now the number one killer of children under five years of age. In addition to achievements described in this issue of Vaccine, the programme has been successful from the US perspective because the working relationships established between the US Department of Health and Human Services' (HHS) Assistant Secretary for Preparedness and Response Biomedical Advanced Research and Development Authority (BARDA) and its partners have assisted in advancing influenza vaccine development at many different levels. A few examples of BARDA's support include: establishment of egg-based influenza vaccine production from "scratch", enhancement of live attenuated influenza vaccine (LAIV) production techniques and infrastructure, completion of fill/finish operations for imported bulk vaccine, and training in advanced bio-manufacturing techniques. These HHS-supported programmes have been well-received internationally, and we and our partners hope the successes will stimulate even more interest within the international community in maximizing global production levels for influenza vaccines.     

A global pandemic influenza vaccine action plan

In case of an influenza pandemic, the world will be in a situation where potential vaccine supply will fall short by several billion doses from global needs. The World Health Organization (WHO) convened in Geneva on May 2-3, 2006 a consultation of all stakeholders in influenza vaccines and immunization to identify practical solutions to fill this gap. The consultation resulted in a global action plan outlining promising specific strategies to increase influenza vaccine production and surge-capacity before and during an influenza pandemic. Although the timing and severity of the next influenza pandemic cannot be predicted, vaccines are considered the one of the most important medical interventions for reducing morbidity and mortality if and when such an event occurs. Despite this acknowledged role, current limitations on influenza vaccine manufacturing capacity mean that, should a pandemic virus emerge in the near future, vaccine supplies would fall short of the anticipated global demand by several billion doses. Concern about this situation was formally acknowledged in May 2005, when the World Health Assembly approved a resolution [1] on strengthening pandemic influenza preparedness and response. That resolution called on the World Health Organization (WHO) to seek solutions with international and national partners, including the private sector, to reduce the present global shortage of influenza vaccines. More specifically, the resolution asked WHO to look at strategies for economizing on the use of antigen and transferring production technologies from industrialized to developing countries. In response to this request, WHO convened a consultation from 2-3 May 2006 attended by representatives of the major stakeholders in the area of influenza vaccines and immunization. The consultation had two main objectives: (1) To prepare a global action plan with specific short-, medium-, and long-term activities designed to increase influenza vaccine production and surge-capacity, to identify key obstacles and driving forces, and to estimate funding needs.(2) To strengthen the engagement and collaboration of key partners and stakeholders.     

An assessment of parental knowledge,attitudes, and beliefs regarding influenza vaccination

IntroductionSeasonal influenza imposes a significant clinical and economic burden. Despite the availability of an annual vaccine to prevent influenza infection and reduce disease severity, influenza vaccination rates remain suboptimal. Research suggests personal experience, perceived effectiveness, and concerns regarding vaccine safety and side effects are the most influential factors in predicting a parent’s decision to vaccinate. However, current literature is primarily focused on the vaccine decision-making of healthcare workers and those at high risk for influenza complications.MethodsTo assess parental attitudes and beliefs regarding the influenza vaccine, a brief mixed-methods survey was developed and optimized for an electronic platform. The Health Belief Model informed survey design and data analysis. Questions were classified into five core concepts: knowledge, barriers, benefits, experience, and severity. Participants were solicited from a population of parents whose children had participated in a school-based influenza surveillance study (n = 244, 73% response rate). We tested associations between responses and children’s influenza vaccination status the prior season. Categorical questions were tested using Pearson's chi-squared tests and numerical or ordered questions using Mann-Whitney tests. P-values were corrected using the Bonferroni method.ResultsDoubting effectiveness, concerns about side effects, inconvenience, and believing the vaccine is unnecessary were barriers negatively associated with parents’ decision to vaccinate their children during the 2017–18 flu season (p < 0.001). Knowledge that the vaccine is effective in lowering risk, duration, and severity of influenza; receiving the influenza vaccine as an adult; and recognizing the importance of vaccination to prevent influenza transmission in high-risk populations were positively associated with parents’ decision to vaccinate (p < 0.001).ConclusionUnderstanding barriers and motivators behind parents’ decision to vaccinate provides valuable insight that has the potential to shape vaccine messaging, recommendations, and policy. The motivation to vaccinate to prevent influenza transmission in high-risk populations is a novel finding that warrants further investigation.     

Development of pandemic influenza vaccine production capacity in Viet Nam

The Institute of Vaccines and Medical Biologicals (IVAC), a state-owned vaccine manufacturer, initiated research into avian influenza vaccines in the early 1990 s in response to the threat of a highly pathogenic avian influenza pandemic. Successful results from laboratory studies on A(H5N1) influenza virus attracted seed funds and led to participation in the WHO technology transfer project to enhance influenza vaccine production in developing countries. IVAC's goal is to produce 500,000 doses of inactivated monovalent whole-virion influenza vaccine per year by 2012, and progressively increase capacity to more than 1 million doses to protect essential populations in Viet Nam in the event of an influenza pandemic. The WHO seed grants, supplemented by other international partner support, enabled IVAC to build in a very short time an influenza vaccine manufacturing plant under Good Manufacturing Practice and relevant biosafety standards, a waste treatment system and a dedicated chicken farm for high-quality eggs. Much of the equipment and instrumentation required for vaccine production has been installed and tested for functional operation. Staff have been trained on site and at specialized courses which provided comprehensive manuals on egg-based manufacturing processes and biosafety. Following process validation, clinical trials will start in 2011 and the first domestic influenza vaccine doses are expected in 2012.     

Passive immunization for influenza through antibody therapies,a review of the pipeline,challenges and potential applications

The Global Action Plan for influenza vaccines (GAP) aims to increase the production capacity of vaccines so that in the event of a pandemic there is an adequate supply to meet global needs. However, it has been estimated that even in the best case scenario there would be a considerable delay of at least five to six months for the first supplies of vaccine to become available after the isolation of the strain and availability of the candidate vaccine virus to vaccine manufacturers. By this time, the virus is likely to have already infected millions of people worldwide, causing significant mortality, morbidity and economic loss.Passive immunization through broadly neutralizing antibodies which bind to multiple, structurally diverse strains of influenza could be a promising solution to address the immediate health threat of an influenza pandemic while vaccines are being developed. These products may also have a role in seasonal influenza as an alternative to other options such as antivirals for the treatment of severe acute respiratory illness due to influenza.This article provides an overview of the current clinical pipeline of anti-influenza antibodies and discusses potential uses and the challenges to product development.     

The 2015 global production capacity of seasonal and pandemic influenza vaccine

A global shortage and inequitable access to influenza vaccines has been cause for concern for developing countries who face dire consequences in the event of a pandemic. The Global Action Plan for Influenza Vaccines (GAP) was launched in 2006 to increase global capacity for influenza vaccine production to address these concerns. It is widely recognized that well-developed infrastructure to produce seasonal influenza vaccines leads to increased capacity to produce pandemic influenza vaccines. This article summarizes the results of a survey administered to 44 manufacturers to assess their production capacity for seasonal influenza and pandemic influenza vaccine production. When the GAP was launched in 2006, global production capacity for seasonal and pandemic vaccines was estimated to be 500 million and 1.5 billion doses respectively. Since 2006 there has been a significant increase in capacity, with the 2013 survey estimating global capacity at 1.5 billion seasonal and 6.2 billion pandemic doses. Results of the current survey showed that global seasonal influenza vaccine production capacity has decreased since 2013 from 1.504 billion doses to 1.467 billion doses. However, notwithstanding the overall global decrease in seasonal vaccine capacity there were notable positive changes in the distribution of production capacity with increases noted in South East Asia (SEAR) and the Western Pacific (WPR) regions, albeit on a small scale. Despite a decrease in seasonal capacity, there has been a global increase of pandemic influenza vaccine production capacity from 6.2 billion doses in 2013 to 6.4 billion doses in 2015. This growth can be attributed to a shift towards more quadrivalent vaccine production and also to increased use of adjuvants. Pandemic influenza vaccine production capacity is at its highest recorded levels however challenges remain in maintaining this capacity and in ensuring access in the event of a pandemic to underserved regions.     

Establishment of pandemic influenza vaccine production capacity at Bio Farma, Indonesia

In Indonesia, avian influenza A(H5N1) virus started to spread in humans in June 2005, with an alarming case-fatality rate of more than 80%. Considering that global influenza vaccine production capacity would barely have covered 10% of the world's pandemic vaccine needs, and that countries with no production facilities or prearranged contracts would be without access to a vaccine, the Government of Indonesia embarked on a programme to increase its readiness for a future influenza pandemic. This included the domestic production of influenza vaccine, which was entrusted to Bio Farma. This health security strategy consists of developing trivalent influenza vaccine production capacity in order to be able to convert immediately to monovalent production of up to 20 million pandemic doses for the Indonesian market upon receipt of the seed strain from the World Health Organization (WHO). For this purpose, a dedicated production facility is being constructed within the Bio Farma premises in Bandung. As an initial stage of influenza vaccine development, imported seasonal influenza bulk has been formulated and filled in the Bio Farma facility. Following three consecutive batches and successful clinical trials, the product was licensed by the Indonesian National Regulatory Authority and distributed commercially for the Hajj programme in 2009. With continued support from its technology transfer partners, Bio Farma is now advancing with the development of upstream processes to produce its own bulk for seasonal and pandemic use.     

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987.In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP.BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees.This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza.     

Pharmacovigilance capacity strengthening for WHO prequalification: The case of the trivalent influenza vaccine manufactured by Instituto Butantan

Instituto Butantan is a biomedical research center and vaccine manufacturer affiliated with the São Paulo State Secretary of Health in Brazil. In 2013, Instituto Butantan successfully licensed its trivalent influenza vaccine, in order to support the Brazilian National Immunization Program's influenza vaccination strategy, which was introduced in 1999. In order to respond to the increasing influenza vaccine demand worldwide, Instituto Butantan is undergoing prequalification of its trivalent influenza vaccine by the World Health Organization (WHO). A key requirement of the prequalification review was the submission of a pharmacovigilance plan, including an active surveillance evaluation, for the trivalent influenza vaccine, and proof of a functional pharmacovigilance system at Instituto Butantan. The aim of this paper is to describe the capacity strengthening process of the pharmacovigilance system at Instituto Butantan for the WHO prequalification of the trivalent influenza vaccine. This process was supported by PATH and the U.S. Federal Government Biomedical Advanced Research and Development Authority (BARDA). The key strategic axes for this capacity strengthening process included the improvement of organizational structure, human resources training, internal processes and procedures, appropriate documentation, and acquisition of an E2B compliant pharmacovigilance database. The project led to the establishment of a functional pharmacovigilance system compliant with international regulatory requirements.     

Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: In vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissive cells

Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAIV) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006–2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.     

我国两个地区儿童流感疫苗与肺炎疫苗接种现状与影响因素分析

目的 了解儿童流感疫苗和肺炎疫苗的接种行为与影响因素。方法 采用两阶段整群抽样,在北京市通州区和甘肃省白银市对适龄儿童家长开展横断面问卷调查,分析儿童流感疫苗和肺炎疫苗接种率及影响因素。结果 共纳入2 377名儿童,儿童流感疫苗接种率为35.93%,肺炎疫苗接种率为16.58%,两种疫苗均接种率为11.65%。接种两种疫苗的理由占比前三位分别为认为疾病严重（流感疫苗：36.02%;肺炎疫苗：49.61%）、学校、单位要求接种（流感疫苗：28.76%;肺炎疫苗：25.45%）和认为疾病易感（流感疫苗：26.41%;肺炎疫苗：13.88%）;未接种疫苗的理由前三位分别为个人方面、疫苗本身和疫苗供应。家庭居住地为农村是影响两类疫苗接种的重要因素。子女数量>1个的家庭、家庭居住地为农村和家庭人均年收入较低与两类疫苗的接种呈负相关。结论 调查地区儿童流感疫苗和肺炎疫苗接种率较低,农村家庭、多子女家庭是扩大疫苗接种的重点关注人群。加强疫苗相关知识宣教,引导家长正确认知疫苗安全性问题,协调疫苗供应与降低疫苗价格对提高流感疫苗和肺炎疫苗接种率具有促进作用。     

A computer simulation of vaccine prioritization,allocation, and rationing during the 2009 H1N1 influenza pandemic

In the fall 2009, the University of Pittsburgh Models of Infectious Disease Agent Study (MIDAS) team employed an agent-based computer simulation model (ABM) of the greater Washington, DC, metropolitan region to assist the Office of the Assistant Secretary of Public Preparedness and Response, Department of Health and Human Services, to address several key questions regarding vaccine allocation during the 2009 H1N1 influenza pandemic, including comparing a vaccinating children (i.e., highest transmitters)—first policy versus the Advisory Committee on Immunization Practices (ACIP)—recommended vaccinating at-risk individuals-first policy. Our study supported adherence to the ACIP (instead of a children-first policy) prioritization recommendations for the H1N1 influenza vaccine when vaccine is in limited supply and that within the ACIP groups, children should receive highest priority.     

Seasonal influenza vaccination in middle-income countries: Assessment of immunization practices in Belarus,Morocco, and Thailand

BackgroundVaccines for the control of seasonal influenza are recommended by the World Health Organization (WHO) for use in specific risk groups, but their use requires operational considerations that may challenge immunization programs. Several middle-income countries have recently implemented seasonal influenza vaccination. Early program evaluation following vaccine introduction can help ascertain positive lessons learned and areas for improvement.MethodsAn influenza vaccine post-introduction evaluation (IPIE) tool was developed jointly by WHO and the U.S. Centers for Disease Control and Prevention to provide a systematic approach to assess influenza vaccine implementation processes. The tool was used in 2017 in three middle-income countries: Belarus, Morocco and Thailand.ResultsData from the three countries highlighted a number of critical factors: Health workers (HWs) are a key target group, given their roles as key influencers of acceptance by other groups, and for ensuring vaccine delivery and improved coverage. Despite WHO recommendations, pregnant women were not always prioritized and may present unique challenges for acceptance. Target group denominators need to be better defined, and vaccine coverage should be validated with vaccine distribution data, including from the private sector. There is a need for strengthening adverse events reporting and for addressing potential vaccine hesitancy through the establishment of risk communication plans. The assessments led to improvements in the countries’ influenza vaccination programs, including a revision of policies, changes in vaccine management and coverage estimation, enhanced strategies for educating HWs and intensified collaboration between departments involved in implementing seasonal influenza vaccination.ConclusionThe IPIE tool was found useful for delineating operational strengths and weaknesses of seasonal influenza vaccination programs. HWs emerged as a critical target group to be addressed in follow-up action. Findings from this study can help direct influenza vaccination programs in other countries, as well as contribute to pandemic preparedness efforts. The updated IPIE tool is available on the WHO website http://www.who.int/immunization/research/development/influenza/en/index1.html.