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Human infections caused by avian influenza A(H7N9) viruses have raised concerns of a pandemic. The capability of the current stockpiled A(H7N9) vaccines to induce cross-protective, nonneutralizing functional antibodies against antigenically drifted A(H7N9) viruses has not been evaluated before. Here we show that vaccination with either MF59- or AS03-adjuvanted inactivated A(H7N9) vaccines elicited robust, cross-reactive antibody-dependent cell-mediated cytotoxicity–mediating and neuraminidase-inhibiting functional antibodies against the antigenically drifted A(H7N9) viruses that emerged recently during the fifth-wave outbreak in China, including a highly pathogenic A(H7N9) human isolate. Such cross-reactive humoral immunity may provide vital first-line defense against fatal outcomes in case of an A(H7N9) pandemic.

In 2005, a year after highly pathogenic avian influenza outbreaks in Thailand, the Thai Government issued a National Strategy Plan for Pandemic Influenza Preparedness, a major objective of which was the domestic production of seasonal influenza vaccine. It was considered that sustained influenza vaccine production was the best guarantee of a pandemic vaccine in the event of a future pandemic. The Government decided to provide funds to establish an industrial-scale influenza vaccine production plant, and gave responsibility for this challenging project to the Government Pharmaceutical Organization (GPO). In 2007, with support from the World Health Organization (WHO), the GPO started to develop egg-based, trivalent inactivated influenza vaccine (IIV) in a renovated pilot plant. In early 2009, during the second year of the project, the GPO turned its attention to develop a pandemic live attenuated influenza vaccine (PLAIV) against the influenza A (H1N1) virus. By December 2010, the H1N1 PLAIV had successfully completed Phase II clinical trials and was awaiting registration approval from the Thai Food and Drug Administration (TFDA). The GPO has also started to develop an H5N2 PLAIV, which is expected to enter clinical trials in January 2011. The next step in 2011 will be the development and clinical evaluation of seasonal LAIV. To meet the needs of the national seasonal influenza vaccination programme, the GPO aims to produce 2 million doses of trivalent IIV in 2012 and progressively increase production to the maximum annual capacity of 10 million doses. This article relates how influenza vaccine production capacity was developed and how major challenges are being met in an expeditious manner, with strong local and global commitment.

•The addition of flu could cripple the health care system during the COVID-19 pandemic.•Fears of coronavirus have intensified the shortage of flu vaccine in developing countries.•We present an optimization model for equitable flu vaccine distribution.•The model utilizes an equitable objective function to distribute vaccines to high-risk people.•We present a case study to exhibit efficacy and demonstrate the model’s applicability. The addition of other respiratory illnesses such as flu could cripple the healthcare system during the coronavirus disease 2019 (COVID-19) pandemic. An annual seasonal influenza vaccine is the best way to help protect against flu. Fears of coronavirus have intensified the shortage of influenza shots in developing countries that hope to vaccinate many populations to reduce stress on their health services. We present an inventory-location mixed-integer linear programming model for equitable influenza vaccine distribution in developing countries during the pandemic. The proposed model utilizes an equitable objective function to distribute vaccines to critical healthcare providers and first responders, elderly, pregnant women, and those with underlying health conditions. We present a case study in a developing country to exhibit efficacy and demonstrate the optimization model’s applicability.

•Annual seasonal vaccine production capacity is estimated at 1.48 billion doses.•Best-case annual production for pandemic vaccine is estimated at 8.31 billion doses.•Modest growth in pandemic influenza vaccine production capacity since 2015.•The majority of production is occurring in High Income Countries.•Challenges remain regarding maintenance of capacity and equitable distribution. Vaccines will be an important element in mitigating the impact of an influenza pandemic. While research towards developing universal influenza vaccines is ongoing, the current strategy for vaccine supply in a pandemic relies on seasonal influenza vaccine production to be switched over to pandemic vaccines. Understanding how much vaccine could be produced, in which regions of the world and in what timeframe is critical to informing influenza pandemic preparedness. Through the Global Action Plan for Influenza Vaccines, 2006–2016, WHO promoted an increase in vaccine production capacity and monitors the landscape through periodically surveying influenza vaccine manufacturers. This study compares global capacity for production of influenza vaccines in 2019 with estimates from previous surveys; provides an overview of countries with established production facilities; presents vaccine production by type and manufacturing process; and discusses limitations to these estimates. Results of the current survey show that estimated annual seasonal influenza vaccine production capacity changed little since 2015 increasing from 1.47 billion to 1.48 billion doses with potential maximum annual influenza pandemic vaccine production capacity increasing from 6.37 billion to 8.31 billion doses. However, this figure should be interpreted with caution as it presents a best-case scenario with several assumptions which may impact supply. Further, pandemic vaccines would not be immediately available and could take four to six months for first supplies with several more months needed to reach maximum capacity. A moderate-case scenario is also presented of 4.15 billion doses of pandemic vaccine in 12 months. It is important to note that two doses of pandemic vaccine are likely to be required to elicit an adequate immune response. Continued efforts are needed to ensure the sustainability of this production and to conduct research for vaccines that are faster to produce and more broadly protective taking into account lessons learned from COVID-19 vaccine development.

[...]they have limited scope for use in older adults in order to limit COVID-19 morbidity and mortality. [...]influenza vaccination could prevent 20% to 60% of influenza infections and thereby potentially a similar percentage of influenza-attributable COVID-19 morbidity and mortality (Table 1). [...]PPV23 use in older adults could prevent up to 33–40% of pneumococcal disease and thereby potentially pneumococcal-attributable COVID-19 morbidity and mortality (Table 1). Despite a potential collateral reduction in influenza and pneumococcal circulation due to contact reducing interventions, in countries where the COVID-19 pandemic coincides with the season of high risk for pneumococcal and/or influenza disease, vaccination at high coverage will have added benefits: minimising the number of pneumococcal and influenza hospital admissions reduces the resources needed to care for non-COVID-19 patients and minimises the risk of health-care acquired COVID-19 infection.

Vaccination against influenza is considered to be one of the key interventions in case of a pandemic. Unfortunately, shortages in vaccine supplies will occur because of the substantial increase in vaccine demands worldwide and the limited available supply resources. The recommended use of monovalent--instead of current trivalent--vaccines containing 15 micro g hemagglutinin (HA) per dose can theoretically triple vaccine volumes but is unlikely to meet the demand. Furthermore, previous experiences demonstrated that one dose of 15 micro g HA will not be sufficient to elicit protective antibody levels in unprimed individuals. Modified formulation approaches were investigated, that would be suitable to provide significantly higher volumes of potent vaccine within a given period of time. Low doses of HA combined with aluminum (Al) adjuvants and the use of whole virus instead of split or subunit antigens can lead to substantial increases in process yield. In addition, production of whole virus vaccines will reduce manufacturing complexity. In a dose-finding study in healthy adults and elderly, immune responses after administration of Al-adjuvanted low-dose formulations were compared to a standard split virus vaccine (Fluarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). All vaccines were safe and well tolerated. Antigen concentrations as low as 1.9 micro g HA/strain per dose of adjuvant-containing experimental vaccines induced protective antibody levels in primed populations. Reactogenicity profiles of Al-adjuvanted low-dose vaccines were investigated in a feasibility trial. Neither the use of Al-adjuvant nor of whole virus had a significant effect on general reactions. Studies in unprimed populations with H2N2 and H9N2 candidate vaccines showed different results, with a potential need for a two-dose schedule. Indeed, hemagglutination inhibition titers did not reach protective levels after a single vaccine dose but could be met following administration of a second dose. The same is true for Al-adjuvanted whole virus formulations with an up to eightfold-reduced antigen content. It may be concluded that the use of Al-adjuvanted whole virus vaccines with low HA content can raise protective antibody levels after two vaccine doses, which may, in turn, result in significant increases of vaccine supplies in the case of a pandemic.

The WHO recommends annual influenza vaccination to prevent influenza illness in high-risk groups. Little is known about national influenza immunization policies globally. The 2014 WHO/UNICEF Joint Reporting Form (JRF) on Immunization was adapted to capture data on influenza immunization policies. We combined this dataset with additional JRF information on new vaccine introductions and strength of immunization programmes, as well as publicly available data on country economic status. Data from countries that did not complete the JRF were sought through additional sources. We described data on country influenza immunization policies and used bivariate analyses to identify factors associated with having such policies. Of 194 WHO Member States, 115 (59%) reported having a national influenza immunization policy in 2014. Among countries with a national policy, programmes target specific WHO-defined risk groups, including pregnant women (42%), young children (28%), adults with chronic illnesses (46%), the elderly (45%), and health care workers (47%). The Americas, Europe, and Western Pacific were the WHO regions that had the highest percentages of countries reporting that they had national influenza immunization policies. Compared to countries without policies, countries with policies were significantly more likely to have the following characteristics: to be high or upper middle income (p<0.0001); to have introduced birth dose hepatitis B virus vaccine (p<0.0001), pneumococcal conjugate vaccine (p=0.032), or human papilloma virus vaccine (p=0.002); to have achieved global goals for diphtheria-tetanus-pertussis vaccine coverage (p<0.0001); and to have a functioning National Immunization Technical Advisory Group (p<0.0001). The 2014 revision of the JRF permitted a global assessment of national influenza immunization policies. The 59% of countries reporting that they had policies are wealthier, use more new or under-utilized vaccines, and have stronger immunization systems. Addressing disparities in public health resources and strengthening immunization systems may facilitate influenza vaccine introduction and use.

For the past few months, the Africa Centres for Disease Control and Prevention (Africa CDC) in Addis Ababa, where we work, has been developing this, with leaders from the African Union and in global health. [...]one of us (J.N.) was working in Côte d'Ivoire as part of a US Centers for Disease Control and Prevention project that was struggling to combat HIV in the country without access to medicine. The World Bank estimates that economic growth in sub-Saharan Africa will decline from 2.4% in 2019 to between -2.1 and -5.1% in 2020, the first recession in the region in 25 years. In August, the African Union Bureau of Heads of State and Government endorsed the strategy put forward by Africa CDC, reiterating how past experience in global health shows that Africa must move decisively, effectively and collectively to secure access to vaccines and life-saving therapy.

Vaccination is a critical part of the response to an influenza pandemic. Future influenza pandemics will likely leverage existing production processes and manufacturing facilities for seasonal influenza to make pandemic vaccines. Therefore, pandemic influenza vaccine response is heavily dependent on seasonal influenza vaccine production capacity. WHO monitors global vaccine production to inform pandemic preparedness by regularly surveying influenza vaccine manufacturers to estimate both seasonal and potential pandemic vaccine production capacity overall and by region, vaccine type, and manufacturing process. The last survey estimates were for 2019; here, we report updated estimates based on data from the 2023 survey and compare to estimates from previous surveys. Our analysis estimates that annual seasonal influenza vaccine production capacity has remained relatively stable since 2019 at 1.53 billion doses and pandemic vaccine capacity at 4.13 and 8.26 billion doses for moderate and best case scenarios, respectively. Over 80 % of seasonal and pandemic vaccine production capacity relies on embryonated eggs, and inactivated influenza virus vaccines comprise the majority of vaccine supply. There is influenza vaccine manufacturing capacity in all WHO regions, except for the African Region, though influenza vaccine production is concentrated in high and upper-middle income countries. The ability to achieve maximum production capacity could be hindered by access to eggs and other ancillary supplies. While influenza vaccine production capacity has been sustained since 2019, significant gaps persist in its distribution, especially in low and lower-middle income countries, and most notably in the African region. This imbalance in production could result in unequal access to vaccines in the event of a pandemic. Strengthening local vaccine manufacturing, promoting seasonal vaccination programmes, and investing in research and development of next-generation influenza vaccines or improved production platforms are essential to improve pandemic preparedness, sustain the influenza vaccine market, and enable more robust local responses.

Seasonal influenza vaccines have the potential to prevent significant morbidity and mortality and the World Health Organization recommends that all countries consider implementing seasonal influenza immunization programmes. These provide invaluable supports to pandemic response, whether through the utilization of influenza epidemiological surveillance systems such as the WHO Global Influenza Surveillance and Response System (GISRS) or RespiMart, by imparting countries with ability to scale up vaccination in response to pandemics, and by contributing to the global production capacity for vaccines. During the COVID-19 pandemic, countries with higher influenza vaccination coverage also achieved higher COVID-19 vaccination coverage. But vaccine hesitancy and complacency are preventing optimal benefits from seasonal influenza vaccination. In 2008, the International Federation of Pharmaceutical Manufacturers and Associations' (IFPMA) Influenza Vaccine Supply International Task Force (IVS) developed a survey method to estimate vaccination coverage rates. The present survey, for 2022 and 2023, highlights that the vast improvements in seasonal influenza vaccination coverage rates achieved during 2020 and 2021 are regrettably not being sustained. Twenty-seven fewer countries in 2022 and 29 fewer countries in 2023 distributed any doses of seasonal influenza than in the peak year for number of countries, 2011. In 2023 there were 17 % fewer vaccine doses distributed globally than in the peak year, 2020. Only 33 of 195 countries achieved the hurdle rate in 2023, defined as number of doses distributed to ≥15.9 % of the population. Governments can strengthen performance of their seasonal influenza vaccination programs with a few key actions. Because immunization returns up to 19 times the cost in societal value, it is critical for governments to identify and implement appropriate countermeasures to vaccine hesitancy and complacency including vaccine advocacy, communications, and communication training for Healthcare Workers. Governments' challenge is to sustain resolve beyond the public health emergency of COVID-19. •A survey method was developed to assess the global distribution of influenza vaccine doses as a proxy for coverage rates.•Compared to 2020 and 2021, the number and rate of distributed seasonal influenza vaccine doses conspicuously declined.•The data highlights that previous improvements in seasonal influenza vaccination coverage rates are not being sustained.•52 % of the global population accessed only 6.2 % of all seasonal influenza vaccine doses distributed in 2023.•Both vaccine hesitancy and complacency demonstrably challenge governments' ability to sustain vaccination coverage.•Governments can undertake policies and actions to counter vaccine complacency and hesitancy.•Sustainable funding, government advocacy, responsive and timely communications, and training of health workers are needed.