New Vaccine Technologies Expand the Frontiers of Prevention and Treatment

Key Takeaways

• Next-generation vaccine development is focused not only on new disease targets but also on broader protection, longer-lasting immunity, fewer doses, improved thermostability, and easier global distribution.

• mRNA vaccine technology, novel adjuvants, needle-free delivery systems, artificial intelligence, and machine learning are among the technologies reshaping vaccine discovery, design, development, and administration.

• Personalized mRNA cancer vaccines are advancing across melanoma, pancreatic cancer, glioblastoma, and other tumor types, while researchers also explore off-the-shelf and preventive cancer vaccine strategies.

• Universal and broad-spectrum vaccines for influenza, coronaviruses, and other respiratory threats aim to provide protection across multiple variants or pathogens and reduce dependence on frequent vaccine reformulation.

• Vaccine candidates targeting tuberculosis and HIV are using advanced antigen design, adjuvant systems, mRNA technology, and immune-targeting strategies to address diseases that have historically been difficult to prevent through vaccination.

• Vaccine research is also expanding into emerging and re-emerging infectious diseases, antimicrobial-resistant pathogens, genital herpes, Lassa fever, and maternal immunization, reflecting a broader approach to pandemic preparedness and global disease prevention.

• Despite funding and public-perception challenges in the United States, vaccine innovation remains a global health priority, increasing the importance of international collaboration, alternative funding, manufacturing capacity, and equitable access.

Despite political headwinds in the United States created by the current administration, vaccine research remains a priority around the world and advances continue to be made. In addition to the development of novel vaccines for challenging diseases that lack effective solutions, improving vaccine performance is a main area of focus. In particular, researchers are seeking to develop multi-virus vaccines, vaccines that provide protection for longer periods with administration of fewer doses, more stable vaccines that are easier to ship because they do not require cold-chain management, and vaccines that can be given at younger ages to prevent diseases later in life.¹

With respect to specific types of vaccines, respiratory viruses (e.g., COVID-19, influenza, respiratory syncytial virus (RSV)) continue to receive significant attention. As climate change impacts virus risks, many researchers are also interested in developing vaccines against “exotic” viruses.² Development of vaccines against antimicrobial resistant pathogens is another priority.³

Artificial intelligence (AI), machine learning (ML), and other digital technologies are becoming increasingly valuable tools for disease modeling, antigen identification, and vaccine design and development.⁴ Continued development of platform manufacturing processes is also anticipated to help reduce costs, even for more specialized vaccines. Underlying all efforts is the drive to increase access globally.

Specific technologies garnering the greatest interest include messenger RNA (mRNA) platforms, novel adjuvants, and innovative delivery approaches, such as needle-free patches.³ Meanwhile, collaborations are helping improve supply and distribution to underserved markets. Examples include the Developing Countries Vaccine Manufacturer Network, with activities in Africa and Latin America, and the Gates Foundation’s support of Biovac, a South African company with the first end-to-end vaccine development program in Africa, starting with oral cholera vaccines.

Despite being a relatively new area of vaccine development — and having $500 million in mRNA vaccine projects cut by the U.S. Department of Health and Human Services, mRNA-based personalized cancer vaccine research continues apace, and numerous candidates are achieving positive results in early clinical trials for patients with skin, non-small cell lung. colorectal, renal cell, bladder. pancreatic, and brain cancers.^5,6 In July 2026, over 130 studies were presented at the American Society of Clinical Oncology meeting in Chicago. Given these early successes, it is not surprising that the World Economic Forum, in conjunction with open science publisher Frontiers, named mRNA cancer vaccines one of the top 10 emerging technologies of 2026.⁷

Moderna alone is testing multiple candidates. The most advanced is intismeran autogen, its personalized neoantigen mRNA cancer vaccine against melanoma, which when administered in combination with Merck’s blockbuster immunotherapy drug Keytruda results in a significantly higher overall 92+% survival rate after five years.⁸ They also reported 74.8% recurrence-free survival at 2.5 years.⁹ Results from a large confirmatory trial may be reported later in the year.

Perhaps most exciting are the results being seen with mRNA vaccines targeting pancreatic cancer, which has historically been difficult to detect and treat, has a five-year survival rate below 12%, and was long thought not to be a candidate for immunotherapy.⁵ BioNTech has an mRNA vaccine (autogene cevumeran) targeting specific mutated proteins in patient tumors that it is investigating in combination with chemotherapy and Genentech’s (Roche's) anti-PDL1 antibody immunotherapy TECENTRIQ^®. In a phase I trials, eight of 16 patients responded to the vaccine, and of those seven were alive up to six years later. A global phase II trial is currently underway to confirm the results.

Advances in lipid nanoparticle (LNP) delivery systems are also having an impact, particularly the ability to enable highly targeted delivery, which results in fewer adverse side effects.⁵ One approach involves the use of LNP clusters rather than individual nanoparticles. This technology was applied in an investigational vaccine against glioblastoma, a fast-growing brain cancer with a five-year survival rate of less than 7%.

There are some big challenges to making personalized mRNA cancer vaccines accessible to all patients. Developing these treatments is expensive. With no opportunity to achieve economies of scale, so is manufacturing personalized products. The first approved treatments could cost as much as $300,000.⁶ New regulatory pathways that evaluate processes rather than products must also be established. To reduce cost, solutions enabling sequencing, vaccine design, and manufacturing to be performed at or near hospitals. There is also hope that once a large number of similar antigens have been identified, development of hybrid off-the-shelf mRNA cancer vaccines may be possible.

On a global basis, tuberculosis (TB) is the leading cause of death from a single infectious agent.¹⁰ The existing vaccine for TB — Bacillus Calmette-Guérin (BCG), developed more than 100 years ago — works well in young children, but the protection declines with age and much less effective in adolescents and adults, who are most likely to get and spread the disease.⁹

There may be a better solution. Vaccine candidate M72/AS01E, developed by GlaxoSmithKline (GSK), achieved approximately 50% efficacy against pulmonary TB in adults with evidence of TB infection in a phase IIb randomized trial with over 3,500 particiapnts.¹¹ Importantly, the vaccine provided protection for more than three years. A phase III trial with 20,000 participants sponsored by the Gates Medical Research Institute (Gates MRI), with funding from the Gates Foundation and Wellcome, is underway to confirm these results. The vaccine consists of a recombinant fusion protein derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A) and GSK’s AS01_E adjuvant system,¹² which is formulated with the two primary immunostimulants 3-O-desacyl-4'-monophosphoryl lipid A and QS-21.¹³ In July 2026, Gates MRI signed an agreement with the Serum Institute of India to manufacture M72/AS01E if the phase III trial results lead to approval of the vaccine candidate.¹¹

Vaccines targeting families of viruses — notably influenza and coronavirus — are progressing through the clinic and may eliminate the need for annual reformulation. The effectiveness of flu vaccines varies each year because they are developed against predicted variants, and the predictions can be more or less accurate. A universal flu vaccine targeting conserved structural regions of the virus should be effective against all variants and thus be effective year after year. Several universal influenza vaccine candidates are currently in clinical trials, with some potentially ready for FDA review in 2029.

Efforts are also underway to develop broad-spectrum vaccines against the coronaviruses, including SARS-CoV-1, MERS-CoV, and SARS-CoV-2. These vaccines are targeting conserved regions (e.g., receptor-binding domain and S2 stem region) of the coronavirus spike protein, providing protection against known and potentially new/emerging variants that could cause future pandemics. Several candidates are in early clinical trials.¹¹

Stanford Medicine researchers have taken the concept of universal vaccines a step further.¹⁴ They have developed an intranasal vaccine that protects mice from respiratory threats including SARS-CoV-2 and other coronaviruses, Staphylococcus aureus and Acinetobacter baumannii (common hospital-acquired infections), and house dust mites (a common allergen). GLA-3M-052-LS+OVA’s universality derives from the fact that it mimics T cell signals that stimulate innate immune cells in the lungs and recruits T cells into the lungs to maintain that response for weeks to months, thereby activating both the innate and adaptive immune responses. The scientists are hoping to initiate a phase I study in humans soon to evaluate the safety of vaccine and then conduct a larger trial in which vaccinated participants (likely two doses) would be exposed to infections.

Developing a vaccine against human immunodeficiency virus (HIV) has been a significant challenge due to its ability to rapidly mutate, leading to genetic diversity and the need for a vaccine to elicit rarely produced broadly neutralizing antibodies.⁴ Researchers are leveraging mRNA technology and a germline targeting strategy to encourage the immune system to make those rare neutralizing antibodies in large quantities.^4,11,15 Priming doses are given to activate rare naïve B cell precursors with the germline features needed to eventually produce broadly neutralizing antibodies. Subsequent heterologous booster doses drive the primed B cells through sequential stages of affinity maturation. The ability to encode multiple complex conformational antigens and rapidly produce modified mRNA constructs makes this approach possible.

Two phase I clinical trials in North America and South Africa/Rwanda conducted by scientific experts at IAVI (International AIDS Vaccine Initiative) and Scripps Research separately investigated the priming and heterologous boosting stages.¹⁶ The results confirmed that the desired immune response (i.e., generation of broadly neutralizing antibodies) can be obtained by giving a series of two doses and that the vaccine is effective in African populations. A third phase I study (IAVI G004) conducted by African investigators was initiated in December 2025 in South Africa to evaluate the safety, immune responses, and dose levels of three different mRNA immunogens (eOD-GT8 60mer, Core-g28v2 60mer, and N332-GT5 gp151) with the hope of achieving desired immune responses st lower doses with reduced risk of adverse reactions, particularly skin issues.¹⁷

Researchers at the University of California, Irvine, are developing a new vaccine for the prevention of genital herpes (caused by herpes simplex virus type 2 (HSV-2)), which affects over 500 million people gobally.¹⁸ Traditional vaccine approaches involving stimulation of antibody production have not been effective. The new mRNA vaccine targets tissue-resident memory T cells in which HSV-2 resides. It uses a “prime/pull/keep” approach: the protective immune cells are primed then directed to infected tissues and maintained there, providing long-term protection. The scientists have shown the vaccine reduces recurrent genital herpes in animal models, increases protective immune responses in target tissues, and leads to recruitment of recruitment and maintenance of protective T cells in those tissues. New funding will allow them to identify an optimal candidate to bring forward to human clinical trials.

Many vaccine candidates targeting a wide range of diseases are being investigated in clinical trials. Examples include:

• DNA-based GNOS-PV01 and peptide-based NeoVax, personalized cancer vaccines for treatment of glioblastoma¹⁹

• NOUS-209, an off-the-shelf neoantigen-directed cancer prevention vaccine designed to train the immune system to recognize and eliminate precancerous and cancerous cells in patients suffering from Lynch Syndrome²⁰

• LASSARAB, a vaccine candidate targeting the viral hemorrhagic illness Lassa fever and rabies, both of which are deadly diseases in West Africa²¹

• A pre-F fusion vaccine against RSV that is administered to pregnant women and protects infants by transferring protective antibodies from mothers to babies before birth⁴

Funding for vaccine research has faced some setbacks recently, particularly in the United States, owing to the nonscientific anti-vaccine outlook of the current administration. Reduced investment levels are having impacts beyond the United States across early discovery to late-stage clinical development. At the World Vaccine Congress U.S. in the spring of 2026, attendees emphasized the fact that vaccine development is a global health priority that must continue, thus making the finding of alternative funding sources and increased international collaboration of growing importance.

In addition to developing novel vaccines for challenging diseases, a significant focus was placed on ensuring proactive preparedness for future pandemics and vigilance against re-emerging diseases, such as polio, that historically were considered to be controlled. Precision neoantigen therapies (e.g., cancer vaccines) were also highlighted.

One of the biggest themes of the event, however, was innovation, both the need for it across all aspects of vaccine development and the tremendous advances that are being made across multiple technology platforms, diseases, and strategies.

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