Collaboration in times of crisis: A study on COVID-19 vaccine R&D partnerships

Collaboration is central for initiatives and efforts in the race to fight COVID-19, with particular focus on fostering rapid development of safe and effective COVID-19 vaccines. We investigated the types of partnerships that have emerged during the pandemic to develop these products. Using the World Health Organization’s list of COVID-19 vaccine developments, we found nearly one third of all vaccine candidates were developed by partnerships, which tended to use next-gen vaccine platforms more than solo efforts. These partnerships vary substantially between materials-transfer partnerships and knowledge-sharing partnerships. The difference is important: The type of sharing between partners not only shapes the collaboration, but also bears implications for knowledge and technology development in the field and more broadly. Policies promoting fair and effective collaboration and knowledge-sharing are key for public health to avoid stumbling blocks for vaccine development, deployment, and equitable access, both for COVID-19 and expected future pandemics.     

Strategies for vaccine-product innovation: Creating an enabling environment for product development to uptake in low- and middle-income countries

Vaccine-product innovations that address barriers to immunization are urgently needed to achieve equitable vaccine coverage, as articulated in the new Immunization Agenda 2030 and the Gavi 5.0 strategy. In 2020, the Vaccine Innovation Prioritisation Strategy (VIPS) prioritized three innovations, namely microarray patches (MAPs), heat-stable and controlled-temperature chain (CTC) enabled liquid vaccine formulations and barcodes on primary packaging. These innovations were prioritized based on the priority immunization barriers that they may help overcome in resource constrained contexts, as well as by considering their potential impact on health, coverage and equity, safety, economic costs and their technical readiness and commercial feasibility. VIPS is now working to accelerate the development and lay the foundation for future uptake of the three priority vaccine-product innovations, with the long term-goal to ensure equitable vaccine coverage and increased impact of vaccines in low- and middle- income countries.To inform our strategic planning, we analyzed four commercially available vaccine product-innovations and conducted interviews with individuals from 17 immunization organizations, and/or independent immunization experts. The findings are synthesized into an ‘innovation conundrum’ that describes the challenges encountered in developing vaccine-product innovations and a vaccine-product innovation ‘theory of change’, which highlights actions that should be undertaken in parallel to product development to incentivize sustainable investment and prepare the pathway for uptake and impact.     

Using geographic information system to track children and optimize immunization coverage and equity in Karachi,Pakistan

BackgroundDespite the potential of geospatial technologies to track and monitor coverage, they are underutilized for guiding immunization program strategy and implementation, especially in low-and-middle-income countries. We conducted geospatial analysis to explore the geographic and temporal trends of immunization coverage, and examined the pattern of immunization service access (outreach and facility based) by children.MethodologyWe extracted data to analyze coverage rates across different dimensions (by enrolment year, birth year and vaccination year) from 2018 till 2020 in Karachi, Pakistan using the Sindh Electronic Immunization Registry (SEIR). We conducted geospatial analysis to assess variation in coverage rates of BCG, Pentavalent (Penta)-1, Penta-3, and Measles-1 vaccines using Government targets. We also analyzed the proportion of children receiving their routine vaccinations at fixed centers and outreach and examined whether children received vaccinations at the same or multiple immunization centers.ResultsA total of 1,298,555 children were born, enrolled or vaccinated from 2018 till 2020. At the district level, analysis by enrollment and birth year showed coverage increased between 2018 and 2019 and declined in 2020, while analysis by vaccination year showed consistent increase in coverage. However, micro-geographic analysis revealed pockets where coverage persistently declined. Notably 27/168, 39/168 and 3/156 Union councils showed consistently declining coverage when analyzing by enrollment, birth and vaccination year respectively. More than half (52.2%, 678,280/1,298,555) of the children received all their vaccinations exclusively through fixed centers and, 71.7% (499,391/696,701) received all vaccinations from the same centers.ConclusionDespite overall improving vaccination coverage between 2018 and 2020, certain geographic areas have consistently declining coverage rates, which is detrimental for equity. Making immunization inequities visible through geospatial analysis is the first step to ensure resources are allocated optimally. Our study provides impetus for immunization programs to develop and invest in geospatial technologies, harnessing its potential for improved coverage and equity.     

Estimating global changes in routine childhood vaccination coverage during the COVID-19 pandemic, 2020–2021

ObjectivesThe COVID-19 pandemic has disrupted the distribution of routine immunizations globally. Multi-country studies assessing a wide spectrum of vaccines and their coverage rates are needed to determine global performance in achieving vaccination goals.MethodsGlobal vaccine coverage data for 16 antigens were obtained from WHO/UNICEF Estimates of National Immunization Coverage. Tobit regression was performed for all country-antigen pairs for which data were continuously available between 2015–2020 or 2015–2021 to predict vaccine coverage in 2020/2021. Vaccines for which multi-dose data were available were assessed to determine whether vaccine coverage for subsequent doses were lower than that of first doses.ResultsVaccine coverage was significantly lower-than-predicted for 13/16 antigens in 2020 and all assessed antigens in 2021. Lower-than-predicted vaccine coverage was typically observed in South America, Africa, Eastern Europe, and Southeast Asia. There was a statistically significant coverage drop for subsequent doses of the diphtheria-tetanus-pertussis, pneumococcus, and rotavirus vaccines compared to first doses in 2020 and 2021.ConclusionThe COVID-19 pandemic exerted larger disruptions to routine vaccination services in 2021 than in 2020. Global efforts will be needed to recoup vaccine coverage losses sustained during the pandemic and broaden vaccine access in areas where coverage was previously inadequate.     

Vaccines: Shaping global health

The Developing Countries Vaccine Manufacturers’ Network (DCVMN) gathered leaders in immunization programs, vaccine manufacturing, representatives of the Argentinean Health Authorities and Pan American Health Organization, among other global health stakeholders, for its 17th Annual General Meeting in Buenos Aires, to reflect on how vaccines are shaping global health. Polio eradication and elimination of measles and rubella from the Americas is a result of successful collaboration, made possible by timely supply of affordable vaccines. After decades of intense competition for high-value markets, collaboration with developing countries has become critical, and involvement of multiple manufacturers as well as public- and private-sector investments are essential, for developing new vaccines against emerging infectious diseases. The recent Zika virus outbreak and the accelerated Ebola vaccine development exemplify the need for international partnerships to combat infectious diseases. A new player, Coalition for Epidemic Preparedness Innovations (CEPI) has made its entrance in the global health community, aiming to stimulate research preparedness against emerging infections. Face-to-face panel discussions facilitated the dialogue around challenges, such as risks of viability to vaccine development and regulatory convergence, to improve access to sustainable vaccine supply. It was discussed that joint efforts to optimizing regulatory pathways in developing countries, reducing registration time by up to 50%, are required. Outbreaks of emerging infections and the global Polio eradication and containment challenges are reminders of the importance of vaccines’ access, and of the importance of new public-private partnerships.     

Ancillary benefits of seasonal influenza vaccination in middle-income countries

While seasonal influenza vaccines (SIV) remain the best method to prevent influenza-associated illnesses, implementing SIV programs may benefit countries beyond disease reduction, strengthening health systems and national immunization programs, or conversely, introduce new challenges. Few studies have examined perceived impacts of SIV introduction beyond disease reduction on health systems; understanding such impacts will be particularly salient in the context of COVID-19 vaccine introduction. We collected qualitative data from key informants—Partnership for Influenza Vaccine Introduction (PIVI) contacts in six middle-income PIVI vaccine recipient countries—to understand perceptions of ancillary benefits and challenges from SIV implementation. Respondents reported benefits associated with SIV introduction, including improved attitudes to SIV among risk groups (characterized by increased demand) and perceptions that SIV introduction improved relationships with other ministries and collaboration with mass media. Challenges included sustaining investment in SIV programs, as vaccine supply did not always meet coverage goals, and managing SIV campaigns.     

The Addis Declaration on Immunization: A binding reminder of the political support needed to achieve universal immunization in Africa

While African countries have improved access to immunization since the start of the millennium, progress has stagnated in the last few years. One in five African children is not vaccinated with life-saving vaccines, and recent outbreaks of vaccine-preventable diseases (VPDs) including yellow fever, measles, and meningitis, among others point to gaps in immunization coverage as well as disease surveillance.In 2017, African Heads of State endorsed the Addis Declaration on Immunization (ADI) at the 28th African Union Summit and committed to ensuring universal access to immunization across the continent. Since then, countries have taken several steps to translate the ADI commitments into tangible progress. However, the continent continues to face challenges in delivering immunization services, including limited vaccine-related funding, inequitable access to immunization services and weak surveillance systems. In the absence of concerted political will, COVID-19 threatens to reverse progress made so far.This paper reflects on the effects of political will in shaping the immunization agenda on the continent and the continued need for political commitment to deliver on the ADI commitments in a post-COVID world. Data were gathered from the regular national immunization reports, WHO/UNICEF estimates of immunization coverage as well as case studies of country implementation on ADI.     

Funding gap for immunization across 94 low- and middle-income countries

Novel vaccine development and production has given rise to a growing number of vaccines that can prevent disease and save lives. In order to realize these health benefits, it is essential to ensure adequate immunization financing to enable equitable access to vaccines for people in all communities. This analysis estimates the full immunization program costs, projected available financing, and resulting funding gap for 94 low- and middle-income countries over five years (2016–2020). Vaccine program financing by country governments, Gavi, and other development partners was forecasted for vaccine, supply chain, and service delivery, based on an analysis of comprehensive multi-year plans together with a series of scenario and sensitivity analyses.Findings indicate that delivery of full vaccination programs across 94 countries would result in a total funding gap of $7.6 billion (95% uncertainty range: $4.6–$11.8 billion) over 2016–2020, with the bulk (98%) of the resources required for routine immunization programs. More than half (65%) of the resources to meet this funding gap are required for service delivery at $5.0 billion ($2.7–$8.4 billion) with an additional $1.1 billion ($0.9–$2.7 billion) needed for vaccines and $1.5 billion ($1.1–$2.0 billion) for supply chain. When viewed as a percentage of total projected costs, the funding gap represents 66% of projected supply chain costs, 30% of service delivery costs, and 9% of vaccine costs. On average, this funding gap corresponds to 0.2% of general government expenditures and 2.3% of government health expenditures.These results suggest greater need for country and donor resource mobilization and funding allocation for immunizations. Both service delivery and supply chain are important areas for further resource mobilization. Further research on the impact of advances in service delivery technology and reductions in vaccine prices beyond this decade would be important for efficient investment decisions for immunization.     

Use of m-Health in polio eradication and other immunization activities in developing countries

IntroductionReaching the children that are chronically missed by routine immunization services has been a key pillar of success in achieving progress toward polio eradication. The rapid advancement and accessibility of mobile technology (“mHealth”) in low and lower middle income countries provides an important opportunity to apply novel, innovative approaches to provide vaccine services. We sought to document the use and effectiveness of mHealth in immunization programs in low and lower middle income countries. We particularly focused on mHealth approaches used in polio eradication efforts by the Global Polio Eradication Initiative (GPEI) to leverage the knowledge and lessons learned that may be relevant for enhancing ongoing immunization services.MethodsIn June 2016, the electronic database PubMed was searched for peer reviewed studies that focused on efforts to improve immunization programs (both ongoing immunization services and supplemental immunization activities or campaigns) through mobile technology in low and lower middle income countries.ResultsThe search yielded 317 papers of which 25 met the inclusion criteria. One additional article was included from the hand searching process. mHealth was used for reminder and recall, monitoring and surveillance, vaccine acceptance, and campaign strategic planning. Mobile phones were the most common mobile device used. Of the 26 studies, 21 of 26 studies (80.8%) reported that mHealth improved immunization efforts.ConclusionmHealth interventions can effectively enhance immunization services in low and lower middle income countries. With the growing capacity and access to mobile technology, mHealth can be a powerful and sustainable tool for enhancing the reach and impact of vaccine programs.     

Impact of vaccine stockouts on immunization coverage in Nigeria

Improving immunization coverage requires creating reliable supply of vaccines and immunization supplies; trained and incentivized health workers; and strategies to improve the demand for immunization. Yet, the interplay of demand and supply side factors on immunization coverage has not been evaluated in literature with data. We use data from Nigeria and a mixed-effects general linear model to estimate the effect of vaccine availability on routine immunization coverage and to identify demand and health system factors which affect this relationship. We find that when vaccine stockouts occur at Local Government Area stores in Nigeria, they significantly decrease the number of children immunized, and for most vaccines, the effect lasts for several months after a stockout. Some of the demand lost when a stockout occurs is recovered over the following six months as children catch up with the regimen. The magnitude of the impact varies across different vaccines.     

The art of partnerships for vaccines

The Developing Countries Vaccine Manufacturers Network (DCVMN) convened vaccine manufacturing experts and leaders from local and global public health organizations for its 19th Annual General Meeting. Lectures and panel discussions centered on international cooperation for better access to vaccines, and partnerships in areas ranging from vaccine research and process development, to clinical studies, regulatory, supply chain and emergency preparedness and response.Global vaccine market trends and changes that will impact vaccine financing and procurement methods were discussed as well as capital sources, including funding, for the development of new or improved vaccines.DCVMN members presented their progress in developing novel Hexavalent, Meningitis, Pneumococcal Conjugate Vaccine, Shigella, Mumps, Rotavirus, Yellow Fever, Polio, Hepatitis E and Dengue vaccines, and a novel monoclonal antibody cocktail for post-bite prophylaxis against rabies infections.Access to and availability of vaccines is enhanced through sharing of best practices for vaccine quality control, reducing redundant testing and promoting development of harmonized common standards. Eligible stakeholders were encouraged to join the WHO-National Control Laboratory Network for Biologicals which serves as a platform for collaboration and technical exchange in this area.Increasing regulatory convergence at the regional and global levels through mechanisms such as joint dossier review and the WHO Collaborative Registration Procedure can help to accelerate vaccine access globally. Additionally, four proposals for streamlining procedures and alignment of dossiers were discussed.Successful partnerships between a broad range of stakeholders, including international organizations, manufacturers, academic research institutes and regulators have provided support for, and in some cases accelerated, vaccine innovation, clinical trials and registration, WHO prequalification, vaccine introduction and access. Strong partnerships, based on experience and trust, help leverage opportunities and are critically important to advancing the shared goal of providing quality vaccines for all people.     

中国脊髓灰质炎疫苗使用历史回顾及免疫策略调整建议

在消灭脊髓灰质炎（脊灰）过程中,脊灰疫苗发挥了重要作用。口服脊灰减毒活疫苗（Oral Poliomyelitis Attenuated Live Vaccine,OPV）是一种安全有效的疫苗,中国于20世纪60年代推广使用OPV,常规免疫接种率逐步提高到〉90％。从1990年开始,部分省（自治区、直辖市）开展了OPV补充免疫活动（Supplementary Immunization Activity,SIA）;1993～2000年,开展消灭脊灰的国家免疫日活动,中国所在的世界卫生组织（World Health Organization,WHO）西太平洋区于2000年实现无脊灰的目标,继续在适龄儿童中加强OPV常规免疫和开展SIA。根据WHO制定的（（2013—2018年消灭脊灰终结战略计划》,2015年所有国家要引进至少1剂灭活脊灰病毒疫苗（Inactivated Poliovirus Vaccine,IPV）,2016年中期使用二价OPV（I＋Ⅲ型）,2018年停用OPV。为确保OPV成功转换IPV,中国应建立部门间协作机制,加快国产IPV研发生产进程,组织开展OPV和IPV转换的相关研究。     

Childhood immunization during the COVID-19 pandemic in Texas

In 2020, the state of Texas implemented coronavirus disease 2019 (COVID-19) social distancing guidelines in order to prevent surges at Texas hospital emergency rooms and in intensive care units. As noted in other states, an unintended consequence of these activities was significant declines in childhood immunizations. After analyzing state-wide immunization register data for Texas, we observed a 47% relative decline in immunization rates between 2019 and 2020 among 5-month-olds and a 58% decline among 16-month-olds. We observed a small decline (5%) among 24-month-olds, and no decline in vaccines received at birth (Hepatitis B). Declines were larger in rural counties compared to urban. These declines are superimposed on increases in state vaccine exemptions over the last five years due to an aggressive anti-vaccine movement in Texas. There are concerns that continued declines in childhood immunization coverage due to COVID-19 could lead to co-endemics of measles and other vaccine preventable diseases.     

Systematic review of cost-effectiveness studies of human papillomavirus (HPV) vaccination: 9-Valent vaccine,gender-neutral and multiple age cohort vaccination

BackgroundThe success of human papillomavirus (HPV) national immunization program depends on effective strategies in optimizing the uptake of HPV vaccine. Given the increasing number of economic evaluations, this review was conducted to update the economic evidence on HPV vaccination, by focusing on: (i) 9-valent vaccine compared to bi- or quadrivalent vaccine; (ii) gender-neutral vaccination compared to female only vaccination; and (iii) multiple age cohort immunization compared to single age cohort immunization.MethodsSearches were performed until June 2016 using 4 databases: PubMed; Embase; Cochrane Library; and LILACS. The combined WHO, Drummond and CHEERS checklist were used to evaluate the quality of included studies.ResultsThirty-four studies were included in the review and most of them were conducted in high-income countries. The inclusion of adolescent boys in vaccination program was found to be cost-effective if vaccine price and coverage was low. When coverage for female was above 75%, gender-neutral vaccination was less cost-effective than when targeting only girls aged 9–18 years. Current evidence does not show conclusive proof of greater cost-effectiveness of 9-valent vaccine compared to the older HPV vaccines as the price for 9-valent vaccine was still uncertain. Multicohort immunization strategy was cost-effective in the age range 9–14 years but the upper age limit at which vaccination was no longer cost-effective needs to be further investigated. Key influential parameters identified were duration of vaccine protection, vaccine price, coverage, and discounting rates.ConclusionsThese findings are expected to support policy-makers in making recommendations for HPV immunization programs on either switching to the 9-valent vaccine or inclusion of adolescent boys’ vaccination or extending the age of vaccination.     

“They're trying to bribe you and taking away your freedoms”: COVID-19 vaccine hesitancy in communities with traditionally low vaccination rates

Vaccination is an essential public health intervention to control the COVID-19 pandemic. A minority of Canadians, however, remain hesitant about COVID-19 vaccines, while others outright refuse them. We conducted focus groups to gauge perceptions and attitudes towards COVID-19 vaccines in people who live in a region with historically low rates of childhood vaccination. Participants discussed their perception of COVID-19 vaccines and their intention to get vaccinated, and the low rate of COVID-19 vaccine uptake in Manitoba’s Southern Health Region compared to other regions in Canada. We identified three drivers of vaccine hesitancy: (1) risk perceptions about COVID-19 and the vaccines developed to protect against it, (2) religious and conservative views; and (3) distrust in government and science. Participant proposed recommendations for improving communication and uptake of the COVID-19 vaccines included: public health messages emphasising the benefits of vaccination; addressing the community’s specific concerns and dispelling misinformation; highlighting vaccine safety; and emphasising vaccination as a desirable behaviour from a religious perspective. Understanding the specific anxieties elicited by COVID-19 vaccines in areas with low childhood immunization rates can inform risk communication strategies tailored to increase vaccination in these specific regions. This study adds important information on potential reasons for vaccine hesitancy in areas with historically low rates of childhood vaccination, and provides important lessons learned for future emergencies in terms of vaccine hesitancy drivers and effective risk communication to increase vaccine uptake.     

The first national adult immunization summit 2012: Implementing change through action

To address lagging vaccine coverage among adults in the United States, over 150 organizations representing a wide range of immunization partners convened in Atlanta, GA from May 15–16, 2012 for the inaugural National Adult Immunization Summit. The meeting called for solution-oriented discussion toward improving current immunization levels, implementing the 2011 National Vaccine Advisory Committee adult immunization recommendations, and capitalizing on new opportunities to improve coverage. Provisions in the federal health reform law that increase access to preventive services, including immunizations, and the increasing numbers of complementary vaccine providers such as pharmacists, create new opportunities to increase access for immunization services and improve coverage for adults. The Summit organized around five focal areas: empowering providers, quality and performance measures, increasing access and collaboration, educating patients, and informing decision-makers. These focal areas formed the basis of working groups, charged to coordinate efforts by the participating organizations to address gaps in the current immunization system. Summit participants identified priority themes to address as tasks during the coming year, including better communicating the value of immunizations to increase demand for immunizations, creating a central repository of resources for providers, patients, and others interested in improving adult immunization levels, examining performance and quality measures and evaluating means to use such measures to motivate vaccine providers, increasing engagement with employer and employee groups to increase awareness and demand for vaccinations, improving the use of immunization information systems and electronic health reports, decreasing barriers to all vaccine providers including pharmacists and community vaccinators, decreasing the complexity of the adult vaccine schedule where possible, engaging adult immunization champions and leaders in key sectors, including adult healthcare provider groups, and encouraging more integration of immunization services with other preventive services.     

Advancing innovation for vaccine manufacturers from developing countries: Prioritization,barriers, opportunities

Development of novel vaccines and improving existing vaccines is critical to addressing areas of unmet or under-addressed health needs globally and to improving existing vaccination coverage and equity. However, vaccine innovation is costly and highly complex. To understand how vaccine manufacturers from developing countries approach innovation, a survey was conducted among company members of the Developing Countries Vaccine Manufacturers Network, in collaboration with the Clinton Health Access Initiative. The survey confirmed that vaccine manufacturers from developing countries are committed to vaccine innovation: 95% of respondents have interest in pursuing vaccine innovation, with strategies targeted towards supplying to low- and middle-income countries. Key barriers to innovation were also surveyed, with respondents highlighting challenges regarding access to in-licensing or joint venture partnerships, financing, and regulatory barriers. Opportunities for innovation are also discussed.     

Progress toward sustainable influenza vaccination in the Lao Peoples’ Democratic Republic, 2012–2018

Despite global recommendations for influenza vaccination of high-risk, target populations, few low and middle-income countries have national influenza vaccination programs. Between 2012 and 2017, Lao PDR planned and conducted a series of activities to develop its national influenza vaccine program as a part of its overall national immunization program. In this paper, we review the underlying strategic planning for this process, and outline the sequence of activities, research studies, partnerships, and policy decisions that were required to build Laos’ influenza vaccine program. The successful development and sustainability of the program in Laos offers lessons for other low and middle-income countries interested in initiating or expanding influenza immunization.     

Planning for COVID-19 vaccines safety surveillance

COVID-19 vaccines are the most important tool to stem the pandemic. They are being developed with unprecedented global collaboration and accelerated timelines to achieve WHO Emergency Use Listing, while using regulatory pathways through national regulatory authorities. Alongside preparations to ensure equitable access to the vaccines among people globally, preparations must be made within countries for COVID-19 vaccines safety surveillance on an urgent basis. Safety surveillance must be capable of investigating adverse events of special interest (AESI) and adverse events following immunization to determine a change in the benefit-risk profile of the vaccine, and to be able to anticipate coincidental events that might be attributed to the vaccine.Active surveillance systems should calculate the incidence of background rates of AESI prior to vaccine roll out. These background rates vary tremendously across regions, populations and case ascertainment methods. Active surveillance systems must be established or strengthened now, (including in LMIC), to calculate the background rates. Utilizing standardized case definitions and global standards for AESI will help in harmonization. Vaccine safety communication plans should be developed. Expanding the global vaccine safety system to meet the needs of COVID-19 and other emergency and routine use vaccines is a priority currently.