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Research and innovation have been fundamental to many of the successes in immunization thus far, and will play important roles in the future success of Immunization Agenda 2030 (IA2030). Strategic Priority 7 (SP7) of IA2030, which addresses research and innovation, is explicitly informed by country needs and priorities, and aims to strengthen the innovation ecosystem through capacity building and collaboration at country, regional, and global levels. SP7 identifies four key focus areas: (1) "needs-based innovation", (2) "new and improved products, services, and practices", (3) "evidence for implementation", and (4) "local capacity". Strategic interventions in these key focus areas apply the lessons of the Global Vaccine Action Plan and the "Decade of Vaccines" to emphasize local innovation, promote the use of research by countries to improve program performance and impact, and encourage capacity building for the development and implementation of innovations. The proposed approach will maintain a focus on the development of new vaccines and the improvement of existing vaccines, and increase attention to innovation in service delivery. Monitoring and evaluation will foster evidence-based priority setting at the country level and help to ground the global research and development (R&D) agenda in the needs of communities. Together, these approaches are intended to harness the power of research and innovation more effectively, to meet the challenges of the future and achieve the ambitious goals of IA2030., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

The WHO/MPP mRNA Technology Transfer Programme, initiated in 2021, focuses on establishing mRNA vaccine manufacturing capacity in LMICs. On 17-21 April 2023, Programme partners were convened to review technology transfer progress, discuss sustainability aspects and promote mRNA product development for diseases relevant to LMICs. To help guide product development, this report introduces key considerations for for understanding the likelihood of technical and regulatory success and of policy development and procurement for mRNA vaccines to be developed and manufactured in LMICs. The report underscores the potential for LMICs to establish sustainable mRNA R&D pipelines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Kristine Moore, Julia Ostrowsky, Angela Mehr, Michael Osterholm report financial support was provided by Wellcome Trust. Kristine Moore, Michael Osterholm report a relationship with Wellcome Trust that includes: funding grants. Coauthor received grants to the organization from Sanofi Pasteur, received grants from US CDC, PATH, Wellcome Trust, South African MRC. (CC) Coauthor is a former Director of one of the WHO International Reference Centres for influenza and was part of the biannual strain selection group. His family superannuation fund holds some shares in companies which produce vaccines, including Influenza vaccine (Pfizer, Merck and CSL) and specific antiviral agents (Vaxart). (IG) Coauthor is an independent Director of two organisations that support vaccine development, the Coalition for Epidemic Preparedness Innovations and MSD Wellcome Trust Hilleman Laboratories Pvt; Ltd. Neither is working on influenza vaccines. (GK) Coauthor has the following declarations: The Icahn School of Medicine at Mount Sinai has filed patent applications relating to universal influenza virus vaccines, SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which name me as inventor. I would also like to note the following, which could be perceived as a conflict of interest: I have previously published work on influenza virus vaccines with S. Gilbert (University of Oxford); have consulted for Curevac, Merck and Pfizer (before 2020); I am currently consulting for Pfizer, Seqirus and Avimex; my laboratory is collaborating with Pfizer on animal models of SARS-CoV-2 and with Dynavax on influenza virus vaccines; my laboratory is collaborating with N. Pardi at the University of Pennsylvania on mRNA vaccines against SARS-CoV-2 and my laboratory was working in the past with GlaxoSmithKline on the development of influenza virus vaccines and two of my mentees have recently joined Moderna. (FK)]., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Every two years, the Global Vaccine and Immunization Research Forum takes stock of global research in vaccines and immunization. As in prior years, the 2018 meeting addressed vaccine discovery, development, decision-making, and deployment. This time, however, it also featured two overarching themes: "Innovating for Equity" and "End-to-End Integration." Significant advances have been made in the last two years, but participants noted that some important goals of the Global Vaccine Action Plan are not being met and called urgently for innovation in improving access to vaccines. Two factors were highlighted as crucial to improving coverage: a focus on equity and sustainability throughout the immunization ecosystem, and an enabling political environment that prioritizes health and immunization., (Published by Elsevier Ltd.)

The respiratory syncytial virus causes a considerable respiratory disease burden globally, most markedly in young infants, in low and middle income countries. A diverse product pipeline illustrates the recent intensification of research and development activities for vaccines and monoclonal antibodies against RSV. With the aim to ensure that product development activities are directed to address the public health needs, the World Health Organization has developed a research and development technical roadmap and articulated product characteristics preferences., (Copyright © 2017. Published by Elsevier Ltd.)

Group B streptococcus, found in the vagina or lower gastrointestinal tract of about 10-40% of women of reproductive age, is a leading cause of early life invasive bacterial disease, potentially amenable to prevention through maternal immunization during pregnancy. Following a consultation process with global stakeholders, the World Health Organization is herein proposing priority research and development pathways and preferred product characteristics for GBS vaccines, with the aim to facilitate and accelerate vaccine licensure, policy recommendation for wide scale use and implementation., (Copyright © 2017. Published by Elsevier Ltd.)

Developing country vaccine manufacturers (DCVMs) supply over half of the vaccines used in developing country immunisation programs. Decisions by developing countries to establish vaccine manufacturing should be based on economic viability, however reliable assessments of vaccine production costs are lacking. This study aimed to quantify the cost of establishing vaccine manufacturing facilities and producing vaccines in developing countries. This study estimates vaccine production costs in developing countries based on twelve vaccines produced by eight DCVMs. The results were based on estimates of the capital and operating costs required to establish vaccine manufacturing facilities under three hypothetical scenarios of production scale and scope. Cost patterns were then compared to vaccine prices paid by countries in both industrialized and developing country markets. The cost of producing vaccines in developing countries was estimated to be on average US$ 2.18 per dose, ranging between US$ 0.98 and US$ 4.85 for different vaccine types and formulations. Vaccine costs-per-dose decrease as production scale and scope increase. Cost-per-dose is mainly driven by fixed costs, but at a scale of production over 20 million doses per year it becomes driven by variable costs. Under the three hypothetical scenarios used, costs-per-dose of vaccines produced by developing countries were around 47% lower than vaccine prices in developing-country markets and 84% lower than prices in industrialized-country markets. This study has found that local production of vaccines in developing countries exhibits both economies of scale and economies of scope. The lower costs relative to prices suggests that a producer surplus and potential profits may be attainable in both developing and developed country markets, supporting sustainable production., (Copyright © 2018 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

In high-income countries, there is an increased tendency to replace inactivated seasonal trivalent influenza (TIV) vaccines with quadrivalent (QIV) vaccines as these are considered to give a greater public health benefit. In addition, several recent studies from the USA and Europe indicate that replacement with QIV might also be cost-effective; however, the situation in low- and middle-income countries (LMIC) is less clear as few studies have investigated this aspect. The paper by de Boer et al. (2008) describes a dynamic modelling study commissioned by WHO that suggests that in LMICs, under certain conditions, QIV might also be more cost-effective than TIV. In this commentary, we discuss some important aspects that policymakers in LMICs might wish to take into account when considering replacing TIV by QIV. Indeed, from the data presented in the paper by de Boer et al. it can be inferred that replacing QIV for TIV would mean a 25-29% budget increase for seasonal influenza vaccination in South Africa and Vietnam, resulting in an incremental influenza-related health impact reduction of only 7-8% when a 10% symptomatic attack rate is assumed. We argue that national health budget considerations in LMIC might lead decision-makers to choose other investments with higher health impact for a budget equivalent to roughly a quarter of the yearly TIV immunization costs. In addition to an increased annual cost that would be associated with a decision to replace TIV with QIV, there would be an increased pressure on manufacturers to produce QIV in time for the influenza season requiring manufacturers to produce some components of the seasonal vaccine at risk prior to the WHO recommendations for influenza vaccines. Unless the current uncertainties, impracticalities and increased costs associated with QIVs are resolved, TIVs are likely to remain the more attractive option for many LMICs. Each country should establish its context-specific process for decision-making based on national data on disease burden and costs in order to determine whether the health gains out-weigh the additional cost of moving to QIV. For example, immunizing more people in the population, especially those in higher risk groups, with TIV might not only provide better value for money but also deliver better health outcomes in LMICs. Countries with local influenza vaccine manufacturing capacity should include in their seasonal influenza vaccine procurement process an analysis of the pros- and cons- of TIV versus QIV, to ensure both feasibility and sustainability of local manufacturing., (Copyright © 2018. Published by Elsevier Ltd.)

Over the past decade, several countries across all regions, income groups and procurement methods have been unable to secure sufficient BCG vaccine supply. While the frequency of stock-outs has remained rather stable, duration increased in 2014-2015 due to manufacturing issues and attracted the attention of national, regional and global immunization stakeholders. This prompted an in-depth analysis of supply and demand dynamics aiming to characterize supply risks. This analysis is unique as it provides a global picture, where previous analyses have focused on a portion of the market procuring through UN entities. Through literature review, supplier interviews, appraisal of shortages, stock-outs and historical procurement data, and through demand forecasting, this analysis shows an important increase in global capacity in 2017: supply is sufficient to meet forecasted BCG vaccine demand and possibly buffer market shocks. Nevertheless, risks remain mainly due to supply concentration and limited investment in production process improvements, as well as inflexibility in demand. Identification of these market risks will allow implementation of risk-mitigating interventions in three areas: (1) enhancing information sharing between major global health actors, countries and suppliers, (2) identifying interests and incentives to expand product registration and investment in the BCG manufacturing process, and (3) working with countries for tighter vaccine management., (Copyright © 2017. Published by Elsevier Ltd.)

Background: The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost., Methods: This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18-49 years with a computer generated randomisation sequence (blocks of six) to receive either two intranasal doses (0·25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart. For part 2, an open-label trial was done in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0·5 mL) of H5N1 booster vaccine. Participants, investigators, and site-study workers were blinded from randomisation. Immune responses after subsequent immunisation were evaluated using haemagglutination-inhibition and microneutralisation assays and circulating follicular T-helper cells and plasmablast cells were measured in serum and whole blood. The trials are registered with ClinicalTrials.gov, numbers NCT01841918 and NCT02229357., Findings: Between Feb 4, 2013, and Feb 28, 2013, 256 individuals were screened, of whom 152 participants were enrolled in part 1 of this study. LAIV H5N2 vaccine was well tolerated. Viral shedding was detected in only six (6%) of 101 participants in the vaccine group 1 day after the first vaccination and in and two (2%) of 98 participants in the group after the second vaccination. There was no serious adverse event in both groups. 51 (50%) of 101 participants in the vaccine group and 28 (55%) of 51 in the placebo group reported at least one adverse event. 80 (84%) of 95 events in the vaccine group and 32 (78%) of 43 events in the placebo groups were reportedly suspected adverse events, probably related to the vaccine; however, most were mild in nature. After two doses of vaccine, 13 (13%) of 100 participants in the vaccine group had an increase in haemagglutination-inhibition titre of more than four-fold and four (4%) of 100 vaccinees developed a rise in neutralisng antibody titre of more than four-fold. 1 year later, after a booster with an inactivated H5N1 vaccine (part 2), 39 (98%) of 40 participants who had previously been vaccinated with LAIV H5N2 had an increase in haemagglutination-inhibition titre of greater than four-fold as early as day 7 compared with three (15%) of 20 participants in the placebo group. Peak geometric mean titre (GMT) for haemagglutination-inhibition antibodies in the previously LAIV H5N2 vaccinated group (566·89 [95% CI 436·97-735·44]) were significantly higher than among those who previously received placebo (25·49 [11·82-54·96]; p<0·0001). The peak GMT by neutralising antibody assay in the H5N2 vaccinated group (1395·85 [1040·79-1872·03]) was also significantly higher than that observed in the placebo group (17·41 [9·05-33·48]; p<0·0001). Importantly, higher cross-reactive haemagglutination-inhibition antibody titres against H5N1 (clades 1, 2.1.3.2, and 2.3.4) were detected in the LAIV H5N2 experienced group than the naive group (p<0·0001)., Interpretation: Our data suggest that LAIV vaccination induces long-lasting memory immune responses. The limitation of this study was that part 2 was designed as a proof-of-concept study by contrast with part 1., Funding: WHO., (Copyright © This is an Open Access article published under the CC BY 3.0 IGO license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products, or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

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., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Should a highly pathogenic avian influenza virus, such as the H5N1 virus type currently circulating in birds, become transmissible among humans, an effective vaccine, rapidly available in vast quantities, would be the best tool to prevent high case-fatalities and the breakdown of health and social services. The number of vaccine doses that could be produced on demand has risen sharply over the last few years; however, it is still alarmingly short of the 13 billion doses that would be needed if two doses were required to protect fully the world's population. Most developing countries would be last in the queue to benefit from a pandemic vaccine. The World Health Organization, together with governments, the pharmaceutical industry and other stakeholders, has been implementing the global pandemic influenza action plan to increase vaccine supply since 2006. Building capacity in developing countries to manufacture influenza vaccine is an integral part of this plan, as well as research and development into more efficacious technologies, e.g. those that allow significant dose-sparing. To this end, the influenza vaccine technology transfer initiative was launched in 2007 and, to date, vaccine manufacturers in 11 developing countries have received grants to acquire the capacity to produce inactivated or live attenuated influenza vaccine for their populations. In addition, a centralized 'hub' has been established to facilitate training in the new technologies for scientists and regulators in the countries. This supplement of Vaccine is devoted to showcasing the interim results of the WHO initiative and the impressive progress made by the developing country manufacturers., (Copyright © 2011 World Health Organization. Published by Elsevier Ltd.. All rights reserved.)

The use of inactivated poliovirus vaccines (IPV) will be required to achieve, world-wide eradication of polio. The current expense of IPV is however prohibitive for, some countries, and therefore efforts to decrease the costs of the vaccine are a high, priority. Our results show that the addition of oil-in-water emulsion adjuvants to an, inactivated trivalent poliovirus vaccine are dose-sparing and are capable of enhancing, neutralizing antibody titers in the rat potency model., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

A number of laboratories around the world are producing Plasmodium falciparum erythrocyte-stage vaccine candidates in the pursuit of a vaccine against clinical malaria disease. These candidates are often based on the same parasite protein. Rigorous clinical development and testing of multiple candidates is limited by available resources, which underscores the need to conduct comparative studies of the different vaccine candidates. The purpose of this study was to compare five different candidate proteins all based on P. falciparum merozoite surface protein-1 (MSP1). After investigators submitted their candidates, basic protein profiles were evaluated in a blinded fashion by an independent laboratory, and groups of rabbits were immunized with the proteins. Sera obtained from the rabbits were compared for antibody titers by ELISA and for functional activity by an in vitro parasite growth inhibition assay (GIA) activity, again in a blinded fashion. In selected cases the fine specificity of the antibodies was assessed. Significant differences in immunogenicity as well as the functional activity of antibodies induced by the various vaccine candidates were noted. Data from this study can assist in making decisions for further clinical development of MSP1-based candidates, and this process sets a precedent for future comparisons of malaria vaccine candidates.

Transcutaneous immunisation (TCI) using a skin patch is a non-invasive vaccination route relevant to mass vaccination against infectious diseases. This phase I/II clinical study, documents that TCI of human adult volunteers with the live-attenuated measles vaccine ROUVAX((R)) is safe and poorly reactogenic. It promotes induction of measles-specific salivary IgA and a tendency to increased frequency of MV-specific IFNgamma-producing T cells. However, in contrast to the subcutaneous route, TCI failed to evoke neutralising MV-specific serum antibodies. Thus, alternative delivery methods and/or devices providing optimal uptake by skin DC should be considered for live-attenuated virus vaccines, such as the measles vaccine.

The last several years have seen significant progress in the development of vaccines against malaria. Most recently, proof-of-concept of vaccine-induced protection from malaria infection and disease was demonstrated in African children. Pursued by various groups and on many fronts, several other candidate vaccines are in early clinical trials. Yet, despite the optimism and promise, an effective malaria vaccine is not yet available, in part because of the lack of understanding of the types of immune responses needed for protection, added to the difficulty of identifying, selecting and producing the appropriate protective antigens from a parasite with a genome of well over five thousand genes and to the frequent need to enhance the immunogenicity of purified antigens through the use of novel adjuvants or delivery systems. Insufficient clinical trial capacity and normative research functions such as local ethical committee reviews also contribute to slow down the development process. This article attempts to summarize the state of the art of malaria vaccine development.