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A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Influenza Virus Vaccines".

Deadline for manuscript submissions: closed (31 March 2026) | Viewed by 19094

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Special Issue Editors

Dr. Francisco Nogareda

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Guest Editor

Special Program Comprehensive Immunization, Pan American Health Organization (PAHO)/World Health Organization (WHO), Washington, DC 20037, USA
Interests: respiratory diseases

Dr. Shoshanna Goldin

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Guest Editor

World Health Emergencies Program, World Health Organization (WHO), 1211 Geneva, Switzerland
Interests: pandemic influenza vaccination

Special Issue Information

Dear Colleagues,

As Dr Tedros Ghebreyesus, Director-General of the World Health Organization, says, “When the next pandemic comes knocking—and it will—we must be ready to answer decisively, collectively, and equitably”. Avian influenza viruses, particularly the influenza A/H5 subtype, pose a significant risk of potential pandemics due to their ability to infect humans and other mammals. While human infections are rare, these viruses' high mutation rate raises concerns about their potential to adapt for efficient human-to-human transmission. Pandemic influenza vaccines are crucial tools in mitigating the impact of influenza pandemics. These vaccines can also play an important role during the interpandemic period to prevent zoonotic infection with H5 viruses in populations at elevated risk and to respond to isolated outbreaks. The 2009 influenza pandemic and the more recent COVID-19 pandemic have highlighted the importance of pandemic planning and preparedness; this includes having an updated national pandemic plan as well as a deployment and vaccination plan. This also includes strengthening national capacities for the early detection, research, regulatory approval, rollout, and monitoring of pandemic influenza vaccinations. These capacities are crucial for an effective and timely response to an influenza pandemic. In light of the above, this Special Issue will have two significant emphases: 1. the development, production, licensing, and procurement of influenza vaccines, and 2. influenza vaccinations during epidemics and pandemics, including preparing for and delivering successful campaigns.

Dr. Francisco Nogareda
Dr. Shoshanna Goldin
Guest Editors

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Keywords

pandemic influenza
vaccines
zoonotic influenza
influenza A/H5
preparedness
response

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Published Papers (9 papers)

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Research

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21 pages, 3237 KB

Open AccessArticle

Investigation of Potential Cross-Protection Conferred by the Seasonal Influenza Vaccine Against Swine Influenza A Viruses of Pandemic Potential

by Alice Lilley, Chiara Chiapponi, Alice Prosperi, Ana Moreno, Laura Soliani, Nicola Lewis and Ruth Harvey

Vaccines 2026, 14(3), 211; https://doi.org/10.3390/vaccines14030211 - 26 Feb 2026

Viewed by 1431

Abstract

Background/Objectives: Influenza A viruses cause seasonal epidemics of respiratory infections in humans, the severity of which can be mitigated by influenza vaccine use. Influenza A viruses circulating in pigs continue to pose a pandemic threat, as evidenced by the influenza virus that caused the 2009 pandemic, which originated in pigs. To understand the relative risk of emergence of influenza A viruses from pigs and to assess the potential role of the seasonal influenza vaccine in mitigating this risk, we evaluate the potential cross-protection afforded by the seasonal influenza vaccine against different clades of recently circulating swine influenza A viruses. Methods: The presence of cross-reactive antibodies in pre- and post-vaccination human serum samples was measured in haemagglutination and microneutralisation assays. Representative H1 swine influenza A viruses from different genetic lineages were tested against sera collected after administration of the seasonal influenza vaccine in healthy adult volunteers over a 6-year time-period. Results: Although a clade-dependent boosting of post-vaccination antibody titres was observed, protective titres often failed to be reached. There was heterogeneity in recognition by sera for the contemporary swine influenza A viruses, with the 1C.2.1 clade virus being well recognised in both assays, whilst very low pre- and post-vaccination antibody titres were observed against the 1A.3.3.2 clade (which emerged in pigs following the reverse zoonotic introduction from humans of the A/H1N1 pdm09 virus) by both assays. Conclusions: Seasonal influenza vaccines produce cross-reactive antibodies against some clades of influenza A viruses circulating in pigs, but not all. Depending on the lineage and clade of the virus, the seasonal influenza vaccine might have utility in the event of a swine variant outbreak in humans, whilst a specific vaccine against the outbreak strain is developed. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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15 pages, 774 KB

Open AccessArticle

Health Worker Influenza Vaccination Programs: A Key to Pandemic Preparedness and Effective COVID-19 Vaccine Deployment in Low- and Middle-Income Countries

by Margaret McCarron, Chelsey Griffin, Tat S Yau, Julie Garon Carlton, Jaymin C Patel, Claire B Hugo, Carsten Mantel, Lindsay B. Saber, Shoshanna Goldin, Ann Moen, Kathryn E Lafond, Jenny A Walldorf, Terri Hyde and Joseph Sewell Bresee

Vaccines 2026, 14(2), 130; https://doi.org/10.3390/vaccines14020130 - 28 Jan 2026

Cited by 1 | Viewed by 1387

Abstract

Background/Objectives: The COVID-19 pandemic presented an urgent global need to quickly vaccinate health workers (HWs). We used this unique circumstance to assess whether mature influenza vaccination programs for HWs facilitated rapid deployment of COVID-19 vaccines in low- and middle-income countries (LMICs). Methods: We used publicly available population-level COVID-19 vaccination coverage data from the World Health Organization (WHO) COVID-19 PowerBI Dashboard for 60 LMICs to investigate general population coverage with the COVID-19 vaccine over the first year of vaccine rollout. We also evaluated country-level policy and program data reported to the WHO–United Nations Children’s Fund (UNICEF) electronic Joint Reporting Form (eJRF) in 2022 or earlier to determine if the presence of a mature (≥2 years of influenza vaccine introduction in HWs prior to 2019) HW influenza vaccination program was associated with more rapid COVID-19 vaccine deployment and/or pandemic preparedness. We used a mixed-effects beta regression model to investigate whether having a mature HW influenza vaccination program was associated with COVID-19 vaccination coverage levels and/or deployment timeliness. Finally, to provide a better understanding of the possible relationship between the presence of a mature HW influenza vaccination program and the COVID-19 vaccine rollout, we analyzed interview data collected during COVID-19 vaccine post-introduction evaluations (cPIEs). Results: Twenty-four of our study countries (40%) had mature HW influenza vaccination programs prior to the COVID-19 pandemic, and 16 (27%) participated in cPIEs. The overall adjusted mean general-population COVID-19 vaccination coverage at 12 months post-deployment in countries with mature HW influenza vaccination programs was 46% (95% CI: (35%, 56%)), compared with 25% (95% CI: (19%, 32%)) in countries without such programs. Vaccination coverage was 2.5 times higher in countries with mature programs (adjusted odds ratio 2.5, 95% CI: (1.5, 4.5); p = 0.001). Conclusions: Our analysis suggests that mature influenza vaccination programs for HWs were associated with timelier and more complete COVID-19 vaccination rollout. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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10 pages, 214 KB

Open AccessArticle

From Seasonal Strategy to Pandemic Shield: The Case for Prioritizing Influenza Vaccination in Long-Term Care

by Jane Barratt, Marco Del Riccio, Stefania Maggi and Jean-Pierre Michel

Vaccines 2025, 13(12), 1211; https://doi.org/10.3390/vaccines13121211 - 30 Nov 2025

Viewed by 974

Abstract

Background: The COVID-19 pandemic exposed both the fragility and importance of long-term care facilities (LTCFs). In this context, seasonal influenza vaccination is more than a routine intervention, it is a measurable indicator of system readiness. Methods: We conducted a secondary analysis of the validated 2022 WHO–UNICEF Joint Reporting Form (JRF) on Immunization for all 194 Member States, extracting (i) policy inclusion of older adults and LTCF residents/staff and (ii) availability of numeric coverage data. Findings were interpreted alongside evidence on vaccine effectiveness and delivery in LTCFs as proxies for operational preparedness. Results: Of 194 countries, 128 (66%) reported a national influenza-vaccination policy. Among these, 109 (56%) recommended vaccination for older adults, while only 84 (43%) explicitly included LTCF residents (few countries explicitly named staff). Numeric coverage for older adults was reported by 54 countries (median 55%, range 0–103%), with 13 meeting the WHO ≥75% target. No country reported specific coverage for LTCF residents or staff. Evidence from trials and observational studies shows that vaccination reduces hospitalisation and mortality among residents and that higher staff uptake is associated with fewer resident infections and improved continuity of operations. Facilities achieving high joint coverage appear to reflect stronger governance, supply chains, data systems, and infection-prevention capacity, the same elements required for pandemic response. Conclusion: Influenza vaccination in LTCFs functions as both a barometer and a mechanism of preparedness. Three practical levers should be recognised as core readiness functions: explicit inclusion of LTCF residents and staff in national policy; routine, public reporting of resident and staff coverage; and timely, resourced on-site delivery before seasonal peaks. Embedding these features would better protect those at highest risk and strengthen overall health-system resilience. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

18 pages, 1422 KB

Open AccessArticle

Sustaining Local Production of Influenza Vaccines: A Global Study of Enabling Factors Among Vaccine Manufacturers

by Christopher Chadwick, Claudia Nannei, Erin Sparrow, William Ampofo, Antoine Flahault and Seth Berkley

Vaccines 2025, 13(11), 1160; https://doi.org/10.3390/vaccines13111160 - 14 Nov 2025

Viewed by 1781

Abstract

Background/Objectives: Local production is a global priority for increasing access to routine, outbreak, and pandemic vaccines and leads to a variety of direct and indirect benefits for countries. This study aimed to characterize the enabling environment for the sustainable production of influenza vaccines, including for epidemic and pandemic preparedness. Methods: National/local vaccine manufacturers were surveyed to capture data on influenza vaccine market contributions, government support for local production, and involvement in national pandemic preparedness activities. Using a conceptual framework for sustainable local production of influenza vaccines for epidemic and pandemic preparedness, manufacturers described 41 global/regional, national, and institutional sustainability factors across policy, health system, research and development (R&D), and regulatory thematic domains. In addition to the survey, key findings from country-level sustainability assessments of vaccine production in Bangladesh, Brazil, Indonesia, Serbia, and Viet Nam were analyzed to complement survey results. Results: This study included 12 participants representing 11 manufacturers from 10 countries. Of the 11 manufacturers, six reported that their countries have policies that support local production, but most manufacturers reported benefiting from some level of direct or indirect support by the government. Manufacturers considered 40/41 factors as important for sustainable production of influenza vaccines, and among the four domains, influenza prevention and control policies, influenza burden data, quality management, and regulatory filing capacity ranked highly. Additionally, manufacturers ranked factors related to cohesive policies for local production promotion and business/strategic planning at the manufacturer level as the top sustainability factors. Conclusions: Manufacturers broadly agreed on the importance of cohesive policies, evidence-based public health priorities, robust R&D and manufacturing investments, and regulatory readiness, though perceptions varied across contexts and company characteristics. Sustainable local production of influenza vaccines should be driven by the alignment of policies, investments, and demand. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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21 pages, 1654 KB

Open AccessArticle

Next-Generation Influenza Vaccines and the Pandemic Horizon: Challenges, Innovations, and the Road Ahead

by Jessica Taaffe, Philipp Lambach, Pierre Gsell, Ioana Ghiga and Shoshanna Goldin

Vaccines 2025, 13(11), 1097; https://doi.org/10.3390/vaccines13111097 - 27 Oct 2025

Cited by 2 | Viewed by 5006

Abstract

Background: Next-generation influenza vaccines have the potential to overcome the limitations of current seasonal influenza vaccines by providing more efficacious, broader, and longer-lasting protection and enhanced pandemic preparedness. However, their development is constrained by regulatory, financial, and scientific challenges. This study aimed to better understand these barriers and enablers from the perspective of vaccine developers. Methods: We employed a mixed-methods approach, collecting data through an online survey and follow-up interviews with 17 developers engaged in next-generation influenza vaccine R&D. Thematic analysis was used to identify key scientific, regulatory, and financial challenges, enablers and priorities for advancing development. Results: Developers reported a range of scientific and regulatory challenges, particularly the lack of established correlates of protection and uncertainty around evaluation criteria for novel platforms. High development costs and limited access to sustained funding were consistently cited as key barriers. Developers emphasized the need for clearer regulatory guidance, harmonized approval pathways, and validation of alternative immune markers. Collaborative approaches, including partnerships, consortia, and trial networks, emerged as critical enablers. Most respondents also reported leveraging their influenza vaccine R&D to support COVID-19 vaccine development, underscoring their relevance to broader pandemic preparedness. Conclusions: Next-generation influenza vaccines have the potential to significantly improve both seasonal influenza control and pandemic response. Realizing this potential requires coordinated action to address scientific, regulatory, and financial hurdles. Investment in regulatory innovation, sustainable financing, and collaborative R&D platforms will be essential to accelerate progress and ensure global access to improved influenza vaccines. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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Review

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14 pages, 851 KB

Open AccessReview

The Road to Readiness: Commentary on the Journey of a Zoonotic H5 Influenza Vaccine Strain Update

by Alexander T. Kennedy, Ray Longstaff, James Fitzpatrick, Clare Hughes, Maria Teresa Malatesta, Raffaella Brandi, Joanne Beighton, Eve Versage, Nedzad Music, Howard Xu, Monica Pagni, Matthew Hohenboken and Beverly Taylor

Vaccines 2026, 14(3), 203; https://doi.org/10.3390/vaccines14030203 - 25 Feb 2026

Viewed by 1030

Abstract

This commentary provides an overview of the development of a zoonotic influenza vaccine, in response to the emergence of an H5N1 subtype virus from clade 2.3.4.4b in mid-2020. When development was initiated, the World Health Organization (WHO) had recommended four candidate vaccine viruses; the A/Astrakhan/3212/2020-like strain was selected as it provided good coverage of circulating viruses and, critically, was available. To facilitate regulatory approval, the licence of an existing zoonotic vaccine, Aflunov (A/turkey/Turkey/01/2005)—a pre-pandemic monovalent A/H5N1 adjuvanted with MF59 and manufactured using the egg-based platform—was duplicated, with the plan to submit a variation to the duplicate licence for the strain update. This was supported by a ferret immunogenicity study using pseudoviruses (allowing the work to be conducted at a lower biosafety level), in conjunction with clinical data from the original Aflunov licence application, and a US study (NCT05874713) on another candidate zoonotic vaccine manufactured using the cell-based platform. Qualification batches for characterisation studies were manufactured at-risk, until calibrated, homologous reagents were available, and the final product release and stability studies were conducted, with rolling provision of stability data to health authorities. The vaccine was initially approved with a shorter shelf-life, allowing early distribution in certain countries, with later extension of the shelf-life once data became available. In terms of procurement and logistics, early consultation between the European Commission and EU member states resulted in the award of a Framework Contract for the initial supply of 665,000 doses to 15 states. Learnings from the development of this vaccine may help to improve pandemic readiness in the future. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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Other

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10 pages, 199 KB

Open AccessPerspective

mRNA and Next-Generation Vaccine Platforms for Pandemic Influenza Preparedness

by Rick A. Bright

Vaccines 2026, 14(3), 247; https://doi.org/10.3390/vaccines14030247 - 7 Mar 2026

Viewed by 2842

Abstract

Pandemic influenza remains a persistent global threat with the potential to cause widespread morbidity, mortality, and economic disruption. Despite decades of preparedness efforts, current influenza vaccine systems remain constrained by long production timelines, early strain-selection requirements, and limited flexibility once a pandemic is underway. The COVID-19 pandemic fundamentally reshaped expectations for vaccine development and deployment, demonstrating that platform-based technologies, particularly messenger RNA (mRNA) vaccines, can deliver safe and effective vaccines at unprecedented speed when supported by regulatory readiness, manufacturing capacity, and coordinated public–private investment. Drawing on lessons from COVID-19, recent Phase III clinical trial data for seasonal influenza mRNA vaccines, and global preparedness initiatives such as the 100 Days Mission, this expert perspective examines how mRNA and other next-generation vaccine technologies could strengthen preparedness for a future influenza pandemic. It reviews evidence related to platform speed, clinical performance, manufacturing adaptability, regulatory pathways, and global access, while also highlighting emerging scientific frontiers, including artificial intelligence–augmented immunogen design and innovations in vaccine delivery. It argues that sustained investment in adaptable vaccine platforms, coupled with advances in delivery, manufacturing, and data-driven design, will be critical to improving global readiness and reducing the impact of the next influenza pandemic. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

10 pages, 490 KB

Open AccessPerspective

Research Priorities for Zoonotic and Pandemic Influenza Vaccines: Evidence and Recommendations from the WHO Public Health Research Agenda for Influenza (2024 Update)

by Wenqing Zhang, Benjamin J. Cowling, John S. L. Tam, Thomas Abraham, Hualan Chen, Keenan Duggal, Wei Xin Khong, Sebastian Maurer-Stroh, Arnold S. Monto, Sergejs Nikisins, Tulio de Oliveira, Yuelong Shu, Cecile Viboud, Richard Webby, Sylvie van der Werf, Jessica Wong and Jean-Michel Heraud

Vaccines 2025, 13(12), 1206; https://doi.org/10.3390/vaccines13121206 - 29 Nov 2025

Cited by 1 | Viewed by 1742

Abstract

Zoonotic influenza viruses, including highly pathogenic avian influenza and swine-origin variants, continue to cause sporadic human infections with, in some cases, high case fatality rates and potential for sustained human-to-human transmission. The COVID-19 pandemic underscored both the possibilities of rapid vaccine innovation and the persistent challenges in equitable access and public trust. This paper synthesizes the vaccine-related priorities from the 2024 update of the World Health Organization Public Health Research Agenda for Influenza, integrating evidence from systematic literature reviews commissioned, expert consultations, and analysis of lessons learned from recent health emergencies, to outline a research and policy roadmap for zoonotic and pandemic influenza vaccine preparedness. Key research priorities identified include development of broadly protective animal and human vaccines; improved understanding of correlates of protection; rapid and scalable manufacturing platforms; predictive modelling for strain selection; and targeted communication strategies to strengthen uptake. Experts have considered that implementing these priorities will require One Health integration, sustained investment, harmonized regulatory frameworks, and proactive community engagement to ensure that advances in vaccine science translate into timely, equitable public health protection. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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16 pages, 529 KB

Open AccessPerspective

Balancing Innovation and Equity: A Successful Dynamic Between Private and Public Sectors Is Essential to Ensure True Pandemic Influenza Preparedness

by Lyn Morgan Marsden and Marie Mazur

Vaccines 2025, 13(11), 1078; https://doi.org/10.3390/vaccines13111078 - 22 Oct 2025

Cited by 1 | Viewed by 1593

Abstract

The COVID-19 pandemic demonstrated both the transformative capacity of vaccine innovation and the persistent inequities that accompany emergency access, underscoring the critical need for stronger collaboration between global health governance and the vaccine industry. Influenza pandemics remain inevitable threats. The continued emergence of avian influenza strains such as H5N1 reinforces the necessity of robust preparedness. This perspective examines the underutilization of private sector vaccine manufacturers in current pandemic influenza frameworks and identifies three central areas where industry participation is indispensable: predictable vaccine demand through robust seasonal influenza programs, economic incentives that de-risk investments in research and development, and diversification of vaccine platforms to expand response capacity. In addition, regionalizing manufacturing, advancing collaborative regulatory models, and negotiating export waivers are presented as potential mechanisms to strengthen equity and supply security. The review highlights demand-based tiered pricing and Advance Purchase Agreements as practical tools to align commercial incentives with public health priorities. Furthermore, it makes the case for embedding private sector representation and knowledge into top-level decision-making and preparedness planning, ensuring investment in innovation is aligned with global health objectives. Ultimately, true pandemic influenza readiness depends on building a sustained seasonal influenza market, embedding private sector engagement into governance structures, and fostering mutual trust to ensure timely access and equitable protection for populations worldwide. Full article

(This article belongs to the Special Issue Pandemic Influenza Vaccination)

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