Racing against COVID-19: a vaccines strategy for Europe. Bruegel Policy Contribution Issue n˚7 | April 2020

The fast development of vaccines is an essential part of the long-term solution to COVID-19, but vaccine development has high costs and carries the risk of high failure rates. There are currently too few promising projects in the clinical trial pipeline to guarantee at least one vaccine soon. More projects need to pass through the development pipeline in parallel. Vaccines should ultimately be widely available to all who need them at low cost. Private life-sciences companies under-invest in vaccine development, especially when compulsory licensing and/or price regulations are imposed. Public funding is needed to reduce the risks of investing in vaccine development, and also to balance compulsory licensing and/or price regulations with incentives for private firms. The public funding being put into identifying COVID-19 vaccines is too limited to carry enough projects through so that at least one vaccine, and preferably more, become available at large scale and low cost. Public budgets for these efforts need to be multiplied up several times over. We propose a staged support scheme to tackle the COVID-19 vaccine challenge and a moon shot programme to meet the challenge of future pandemics. We calculate the public budget needed to ensure supply of COVID-19 vaccines. Although substantial, the budget represents a bargain compared to the avoided health, social and economic costs

Accelerating vaccine development and deployment: report of a Royal Society satellite meeting.

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it

RTS,S/AS02 and the quest of the Holy Grail

High-profile programs under the WHO/Roll Back Malaria initiative, in addition to unravelling the human and malaria parasite genomes, have ensured that malaria vaccine research and development are enjoying an unprecedented boom. So far, the development of a vaccine against such a complex parasite has been elusive. Recently, there have also been concerns that imperfect vaccines could encourage the selection of more virulent parasite strains [1]. However, there is compelling evidence that, if an effective malaria vaccine was developed, it would prove to be protective because several studies have shown that: (1) immunity to malaria can develop of multiple Plasmodium infection; and (2) exposure to bites from irradiated Anopheles infected with Plasmodium falciparum can confer protection against infection for up to 10 months. Based on these findings, effector T-cell vaccines that rate pre-erythrocytic stages of the parasite in infected hepatocytes have been developed

Novel approaches, including systems biology, to HIV vaccine research and development: Report from a Global HIV Vaccine Enterprise Working Group

The Global HIV Vaccine Enterprise convened a two-day workshop on August 10-11 2009, at the Fred Hutchison Cancer Research Center offices in Seattle, WA, to discuss the application of novel approaches,including systems biology, to HIV vaccine research and development. The goals of this Working Group were to identify key scientific issues and opportunities that have emerged since the Enterprise Scientific Strategic Plan1 was published in 2005, and to make recommendations to Enterprise stakeholders

A Vaccine Against Group B Streptococcus: Recent Advances

Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide – protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible

Phase I, randomized, observer-blind, placebo-controlled studies to evaluate the safety, reactogenicity and immunogenicity of an investigational non-typeable Haemophilus influenzae (NTHi) protein vaccine in adults

Background: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD],E [PE] and Pilin A [PilA]) in two observer-blind phase I studies. Methods: In the first study (NCT01657526), 48 healthy 18-40 year-olds received two vaccine formulations (10 or 30 mu g of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50-70 year-olds, current or former smokers, received eight vaccine formulations (10 or 30 mu g antigen/dose non-adjuvanted or adjuvanted with alum, AS01(E) or ASO4(c)) or saline placebo at months 0,2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination. Results: Observed reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses. Conclusion: This study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate

Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines

BackgroundPolymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candidates show substantial polymorphism. However, knowledge on antigenic diversity of key antigens, the impact of polymorphism on potential vaccine escape, and how sequence polymorphism relates to antigenic differences is very limited, yet crucial for vaccine development. Plasmodium falciparum apical membrane antigen 1 (AMA1) is an important target of naturally-acquired antibodies in malaria immunity and a leading vaccine candidate. However, AMA1 has extensive allelic diversity with more than 60 polymorphic amino acid residues and more than 200 haplotypes in a single population. Therefore, AMA1 serves as an excellent model to assess antigenic diversity in malaria vaccine antigens and the feasibility of multi-allele vaccine approaches. While most previous research has focused on sequence diversity and antibody responses in laboratory animals, little has been done on the cross-reactivity of human antibodies.MethodsWe aimed to determine the extent of antigenic diversity of AMA1, defined by reactivity with human antibodies, and to aid the identification of specific alleles for potential inclusion in a multi-allele vaccine. We developed an approach using a multiple-antigen-competition enzyme-linked immunosorbent assay (ELISA) to examine cross-reactivity of naturally-acquired antibodies in Papua New Guinea and Kenya, and related this to differences in AMA1 sequence.ResultsWe found that adults had greater cross-reactivity of antibodies than children, although the patterns of cross-reactivity to alleles were the same. Patterns of antibody cross-reactivity were very similar between populations (Papua New Guinea and Kenya), and over time. Further, our results show that antigenic diversity of AMA1 alleles is surprisingly restricted, despite extensive sequence polymorphism. Our findings suggest that a combination of three different alleles, if selected appropriately, may be sufficient to cover the majority of antigenic diversity in polymorphic AMA1 antigens. Antigenic properties were not strongly related to existing haplotype groupings based on sequence analysis.ConclusionsAntigenic diversity of AMA1 is limited and a vaccine including a small number of alleles might be sufficient for coverage against naturally-circulating strains, supporting a multi-allele approach for developing polymorphic antigens as malaria vaccines

Host Genetics and Viral Diversity: Report from a Global HIV Vaccine Enterprise Working Group

The Global HIV Vaccine Enterprise convened a workshop in September 2009 to discuss human and viral genetic variation and its impact on future directions for HIV vaccine research and development. The formidable challenges presented by virus and host genetic variability are interrelated and complicate vaccine development. HIV vaccine researchers need to develop innovative approaches that will facilitate addressing these questions in novel ways

Acute Respiratory Infections and Child Survival: Potential Role of Pneumococcal vaccine control

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