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Artificial intelligence for translational personalized neoantigen cancer vaccine development.

Personalized neoantigen cancer vaccine is a promising strategy for precision immunotherapy by targeting patient-specific and mutation-derived tumor antigens. Early clinical studies have demonstrated the feasibility, safety, and immunogenicity of these vaccines across multiple solid tumors, with encouraging outcomes particularly when combined with immune checkpoint blockade. However, broader clinical translation remains limited by sequential bottlenecks across the vaccine development pipeline, including false-positive neoantigen selection,  imperfect modeling of antigen processing and HLA presentation, limited prediction of T-cell receptor recognition, and challenges in formulation, delivery, and manufacturing. Artificial intelligence and advanced computational workflows are increasingly integrated into this pipeline to improve candidate prioritization and support more reproducible decision-making. In this review, we summarize clinical progress and key translational barriers in personalized neoantigen vaccination, and discuss how AI-enabled approaches may contribute across four major stages: multi-omics integration for neoantigen discovery, processing-aware HLA presentation prediction, structure-aware and TCR-informed immunogenicity modeling, and data-driven formulation optimization, particularly for lipid nanoparticle-based delivery systems. These approaches are able to help narrow biological and chemical search spaces, improve prioritization, and provide mechanistic insights into antigen presentation and immune recognition rather than replacing experimental validation. This articlefurther addresses future implementation challenges, including dataset diversity, model interpretability, prospective benchmarking, manufacturing traceability, and evolving regulatory frameworks for individualized mRNA cancer immunotherapies. Integrating computational innovation with rigorous immunological validation, scalable manufacturing, and regulatory oversight will be essential for advancing personalized neoantigen vaccines toward broader clinical implementation.

Cancer Vaccines

Intestinal immunity and vaccine development: a WHO memorandum.

As part of the research component of the WHO Diarrhoeal Diseases Control Programme, a Scientific Working Group met in August 1978 to review recent advances in knowledge of intestinal immunity, the application of genetic techniques in enteric vaccine development, the status of currently available immunizing agents against cholera, typhoid fever, and Shigella dysentery, and the prospects for the development of new or improved vaccines against the well known and newly recognized agents such as rotavirus and enterotoxigenic Escherichia coli. In each of these areas, the Group made specific recommendations for further research that should be considered for support under the WHO research programme in the field of diarrhoeal diseases.

Animals

Advancing the fight against tuberculosis: integrating innovation and public health in diagnosis, treatment, vaccine development, and implementation science.

Tuberculosis (TB) remains one of the leading causes of infectious disease mortality worldwide, increasingly complicated by the emergence of drug-resistant strains and limitations in existing diagnostic and therapeutic strategies. Despite decades of global efforts, the disease continues to impose a significant burden, particularly in low- and middle-income countries (LMICs) where health system weaknesses hinder progress. This comprehensive review explores recent advancements in TB diagnostics, antimicrobial resistance (AMR surveillance), treatment strategies, and vaccine development. It critically evaluates cutting-edge technologies including CRISPR-based diagnostics, whole-genome sequencing, and digital adherence tools, alongside therapeutic innovations such as shorter multidrug-resistant TB regimens and host-directed therapies. Special emphasis is placed on the translational gap-highlighting barriers to real-world implementation such as cost, infrastructure, and policy fragmentation. While innovations like the Xpert MTB/RIF Ultra, BPaLM regimen, and next-generation vaccines such as M72/AS01E represent pivotal progress, their deployment remains uneven. Implementation science, cost-effectiveness analyses, and health equity considerations are vital to scaling up these tools. Moreover, the expansion of the TB vaccine pipeline and integration of AI in diagnostics signal a transformative period in TB control. Eliminating TB demands more than biomedical breakthroughs-it requires a unified strategy that aligns innovation with access, equity, and sustainability. By bridging science with implementation, and integrating diagnostics, treatment, and prevention within robust health systems, the global community can accelerate the path toward ending TB.

diagnostic innovation

New approaches to HIV vaccine development.

Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.

AIDS Vaccines

Malaria vaccine development.

Prospects for the development of effective malaria vaccines have greatly improved over the last 15 years. For further progress to be achieved rapidly, the need for clinical research centres, where exposure and re-exposure to infection can be carefully controlled, is paramount. At such centres, it is possible to evaluate the safety and efficacy of vaccine preparations, using different strams and species of parasite, and to undertake studies in both nonimmune and partially immune volunteers. However, as efficacy under these conditions may not be a good indicator of efficacy under other conditions, the results of such studies should be complemented by field trials in endemic areas. It seems probable that vaccines may show degrees of partial effectiveness in relation to different strains, species, intensities of parasite inocula, and hosts.

Animals

Attenuated live fowl cholera vaccine. I. Development of vaccine strain M3G of Pasteurella multocida.

A live cholera vaccine was developed from a virulent avian septicemia strain of Pasteurella multocida serotype 1. The virulent parental strain was mutagenized with N-methyl-N'-nitro-N-nitroso guanidine. Mutants were selected that had either smaller colonies at 37 C or temperature sensitivity for growth at 41 C. Four small-colony mutants and 2 temperature-sensitive mutants were studied. All the mutants were avirulent for turkeys. Sixteen days after turkeys were vaccinated with each mutant, both the vaccinates and unvaccinated controls were challenge-exposed to virulent P. multocida of the homologous serotype and the heterologous serotype 3. Two of the small-colony mutant strains protected against both homologous and heterologous challenge. Suggested for a live cholera vaccine is P. multocida M3G, a small-colony-forming mutant, innocuous for both mice and turkeys and stable against reversion.

Animals

Isolation of a temperature-sensitive dengue-2 virus under conditions suitable for vaccine development.

Dengue virus, type 2, in viremic human sera and after passage in cell cultures produces mixtures of small and large plaques when assayed in LLC-MK2 cells. Clones of dengue virus type 2 obtained by plaque selection in primary green monkey kidney cell cultures were tested for temperature sensitivity in vitro and for virulence by intracerebral inoculation of suckling mice. Sublines of a small-plaque clone were found to have lower nonpermissive temperatures than the parent virus by both plaque formation and release of infectious virus into the culture media. Small-plaque sublines were significantly less virulent in suckling mice than was the parent virus. Sublines from a large-plaque clone were not temperature sensitive and closely resembled parent virus mixed-plaque morphology. When small-plaque sublines were serially passaged using undiluted inocula, reversion occurred as evidenced by the appearance of large plaques and return of mouse virulence. Small-plaque virus could be maintained through several serial passages without reversion by using low-input inocula. Desirable passage history as well as temperature-sensitive and attentuation characteristics of the S-1 small-plaque subline make it appear suitable as a vaccine candidate virus.

Animals

[The development of vaccination as demonstrated on the development of the Bavarian State Vaccination Institute in the 19th and 20th centuries].

In 1801 the smallpox vaccination has been introduced in Bavaria by order of the Duke Franz Joseph. He appointed a Medical Superintendent, responsible for smallpox vaccinations for the whole country. This was the hour of birth for the Institute, too. The Institute developed quickly to a point of crystallization in the field of prophylactic medicine, research on infectious diseases and social pediatrics. By this Institute the "Retrovaccine" against smallpox was introduced 1856. 1967 -- 1976 an attenuated life smallpox-vaccine (MVA) has been developed. Some years ago the activities of the Institute had been focussed into research of complications after vaccinations and up to date, on the pathogenesis of Multiple Sclerosis. A historical review demonstrates the development of the Institute in the past up to modern activities in research, teaching students and postgraduate education and in medical practice.

Academies and Institutes

Recent developments in vaccination against bovine brucellosis.

Recent research in vaccination against bovine brucellosis has been directed towards reducing the serological response to vaccination and to developing serological tests better able to distinguish vaccinal titres from those resulting from field infection. In the case of strain 19 vaccination, developments such as reducing the dose of vaccine and improving serological tests have so reduced the serological response as to allow adult vaccination to be carried out in combination with eradiction by test and slaughter. B. abortus 45/20 vaccine is being increasingly used as a combined diagnostic aid and protective agent. Progress has been made in identifying antibodies produced in response to this vaccine.

Agglutination Tests

Viral vaccines under development: a third generation.

In summary then, my purpose has been two-fold: on the one hand, I have tried to highlight the kinds of basic science advances in both cellular and virologic research that can (and should) be focussed both on vaccines under development and, retrospectively, on those whose origins were strictly empiric. On the other hand, I have attempted a partial survey of some of the prominent members of a potential new generation of vaccines to point out areas where these advances can and should contribute either to progress or to a sense of caution about the further reliance on pure empiricism. It is clear that we are not finished with new viral vaccines. It is equally clear that narrowing the persistent gap between basic science and its application to public health needs will require much energy and attention as vaccine development progresses.

Bioethics

[Assessment of the effectiveness of different methoods of immunization with live plague vaccine EB in aerosol infections].

The work deals with the results of the comparative evaluation of the effectiveness of vaccines developed at the Sanitary Research Institute (Zagorsk) and the Mechnikov Research Institute for Vaccines and Sera (Moscow), as well as two methods of immunization against plague, by inhalation and subcutaneous injection, under the conditions of aerosol infection. The immunogenic effectiveness of both vaccines, when evaluated in terms of LD50, was shown to be approximately the same, but the animals immunized by the inhalation method with the vaccine developed at the Sanitary Research Institute proved to be less susceptible to infection than those immunized with the vaccine developed at the Mechnikov Research Institute for Vaccines and Sera in Moscow. After immunization by the inhalation method the vaccine developed at the Sanitary Research Institute rendered more effective protection (3- to 4-fold) against aerosol infection than after immunization by subcutaneous injection. The animals immunized by the inhalation method proved to be capable of surviving plague in the primary pneumonic form.

Aerosols