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.

BACKGROUND: The pace of global progress must increase if the Global Vaccine Action Plan (GVAP) goals are to be achieved by 2020. We administered a two-phase survey to key immunization stakeholders to assess the utility and application of GVAP, including how it has impacted country immunization programs, and to find ways to strengthen the next 10-year plan. METHODS: For the Phase I survey, an online questionnaire was sent to global immunization stakeholders in summer 2017. The Phase II survey was sent to regional and national immunization stakeholders in summer 2018, including WHO Regional Advisors on Immunization, Expanded Programme on Immunization managers, and WHO and UNICEF country representatives from 20 countries. Countries were selected based on improvements (10) versus decreases (10) in DTP3 coverage from 2010 to 2016. RESULTS: Global immunization stakeholders (n=38) cite global progress in improving vaccine delivery (88%) and engaging civil society organizations as advocates for vaccines (83%). Among regional and national immunization stakeholders (n=58), 70% indicated reaching mobile and underserved populations with vaccination activities as a major challenge. The top ranked activities for helping country programs achieve progress toward GVAP goals include improved monitoring of vaccination coverage and upgrading disease surveillance systems. Most respondents (96%) indicated GVAP as useful for determining immunization priorities and 95% were supportive of a post-2020 GVAP strategy. CONCLUSIONS: Immunization stakeholders see GVAP as a useful tool, and there is cause for excitement as the global immunization community looks toward the next decade of vaccines. The next 10-year plan should attempt to increase political will, align immunization activities with other health system agendas, and address important issues like reaching mobile/migrant populations and improving data reporting systems.

Influenza vaccination remains the most effective tool for reducing seasonal influenza disease burden. Few Low and Middle-Income Countries (LMICs) have robust, sustainable annual influenza national vaccination programs. The Partnership for Influenza Vaccine Introduction (PIVI) was developed as a public-private partnership to support LMICs to develop and sustain national vaccination programs through time-limited vaccine donations and technical support. We review the first 5years of experience with PIVI, including the concept, country progress toward sustainability, and lesson learned. Between 2013 and 2018, PIVI worked with Ministries of Health in 17 countries. Eight countries have received donated vaccines and technical support; of these, two have transitioned to sustained national support of influenza vaccination and six are increasing national support of the vaccine programs towards full transition to local vaccine program support by 2023. Nine additional countries have received technical support for building the evidence base for national policy development and/or program evaluation. PIVI has resulted in increased use of vaccines in partner countries, and early countries have demonstrated progress towards sustainability, suggesting that a model of vaccine and technical support can work in LMICs. PIVI expects to add new country partners as current countries transition to self-reliance.

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.

A century after the great influenza pandemic of 1918, influenza remains a major public health threat. Annual epidemics are associated with significant mortality and morbidity globally, leading to an estimated 290,000–650,000 deaths each year [1]. In addition, the ongoing threat of the next pandemic requires significant resources and attention to ensure that communities and governments are prepared to mitigate the health and societal impact that would likely be much larger than the seasonal toll from influenza [2]. Vaccines against influenza have long been used to reduce seasonal disease risk and to reduce illness and spread of pandemic influenza [3], [4], [5], [6]. However, the variable and moderate effectiveness, the limited ability to prevent influenza caused by antigenically dissimilar challenge viruses, and the complex and lengthy process for semiannual vaccine production, highlight the limitations of current vaccines to optimally address both seasonal and pandemic threats [7], [8], [9], [10]. As a result, growing interest in developing improved influenza vaccines has been voiced by public health authorities and other global stakeholders.

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Background: Immunodeficient individuals who excrete vaccine-derived polioviruses threaten polio eradication. Antivirals address this threat. Methods: In a randomized, blinded, placebo-controlled study, adults were challenged with monovalent oral poliovirus type 1 vaccine (mOPV1) and subsequently treated with capsid inhibitor pocapavir or placebo. The time to virus negativity in stool was determined. Results: A total of 144 participants were enrolled; 98% became infected upon OPV challenge. Pocapavir-treated subjects (n = 93) cleared virus a median duration of 10 days after challenge, compared with 13 days for placebo recipients (n = 48; P = .0019). Fifty-two of 93 pocapavir-treated subjects (56%) cleared virus in 2-18 days with no evidence of drug resistance, while 41 of 93 (44%) treated subjects experienced infection with resistant virus while in the isolation facility, 3 (3%) of whom were infected at baseline, before treatment initiation. Resistant virus was also observed in 5 placebo recipients (10%). Excluding those with resistant virus, the median time to virus negativity was 5.5 days in pocapavir recipients, compared with 13 days in placebo recipients (P < .0001). There were no serious adverse events and no withdrawals from the study. Conclusions: Treatment with pocapavir was safe and significantly accelerated virus clearance. Emergence of resistant virus and transmission of virus were seen in the context of a clinical isolation facility. Clinical Trials Registration: EudraCT 2011-004804-38.

Chronic prolonged excretion of vaccine-derived polioviruses by immunodeficient persons (iVDPV) presents a personal risk of poliomyelitis to the patient as well as a programmatic risk of delayed global eradication. Poliovirus antiviral drugs offer the only mitigation of these risks. Antiviral agents may also have a potential role in the management of accidental exposures and in certain outbreak scenarios. Efforts to discover and develop poliovirus antiviral agents have been ongoing in earnest since the formation in 2007 of the Poliovirus Antivirals Initiative. The most advanced antiviral, pocapavir (V-073), is a capsid inhibitor that has recently demonstrated activity in an oral poliovirus vaccine human challenge model. Additional antiviral candidates with differing mechanisms of action continue to be profiled and evaluated preclinically with the goal of having 2 antivirals available for use in combination to treat iVDPV excreters.