A New Era of Immunization: The Rise of Next-Generation Vaccines

Traditional vaccines, such as live attenuated, inactivated, toxoid, and conjugate formulations, have controlled infectious diseases for decades. However, they face limitations, including long development timelines and complex manufacturing. This often significantly delays vaccine availability and deployment.1

Next-generation platforms build on established vaccine principles to overcome such constraints, enabling faster production, versatile formulations, and operational efficiency, which are key for responding to emerging infectious outbreaks.2,3 These include mRNA vaccines, which deliver messenger RNA to host cells, directing intracellular synthesis of specific antigens and eliciting targeted adaptive immune responses. This approach facilitates rapid vaccine design and production, as the RNA sequence can be modified to address emerging variants or pathogens.3

Another class of next-generation platforms is DNA vaccines. They typically deliver genetic material via plasmids into host cells, where antigens are expressed internally, eliciting both humoral and cellular immune responses, and offering stability for storage and distribution.3

In addition to nucleic acid-based approaches, viral vector vaccines use genetically modified viruses, mainly adenoviruses, to deliver genetic sequences into host cells, inducing a comprehensive immune response. In contrast, protein subunit vaccines contain purified antigens or engineered protein fragments instead of genetic material, targeting specific pathogen components for precise stimulation of the immune system.4,5

Complementing these strategies, nanoparticle-based delivery systems use synthetic carriers, lipid nanoparticles (LNPs), or virus-like particles (VLPs) to enhance vaccine antigens' stability, delivery, and immunogenicity, promoting targeted and durable immune activation. LNPs efficiently encapsulate and deliver nucleic acids for intracellular uptake, whereas VLPs mimic viral structures without genetic material.6

Next-generation vaccines are expanding the scope of immunization, with potential applications beyond traditional infectious disease prevention, addressing acute global health emergencies and therapeutic gaps.

The COVID-19 pandemic represents a prime example, serving as a large-scale validation for next-generation vaccine platforms' rapid development and deployment. mRNA vaccines such as Pfizer-BioNTech’s Comirnaty and Moderna’s Spikevax illustrated the capacity of nucleic acid–based platforms to move from genomic sequencing of SARS-CoV-2 to clinical evaluation within weeks (~9 weeks is the reported approximate timeline) while achieving high efficacy in pivotal trials.5,7

Other pharma companies also contributed to novel COVID-19 vaccine development. AstraZeneca/Oxford and Johnson & Johnson produced viral vector vaccines using replication-deficient adenoviruses as alternative delivery mechanisms, while Novavax developed a protein subunit vaccine based on recombinant spike protein combined with a saponin-based adjuvant to elicit immune responses.5

Next-generation vaccine technologies have also been leveraged for longstanding infectious diseases such as malaria, which remains a major global health burden, particularly in endemic regions.

The protein subunit vaccine RTS,S/AS01 was the first to demonstrate clinical efficacy against Plasmodium falciparum and has been incorporated into routine immunization programs in several African countries. Research continues with complementary strategies, including viral vector platforms such as ChAd63-MVA RH5, which seek to enhance protection and durability while addressing variable immune responses and ensuring long-term efficacy in high-transmission settings.8,9

Respiratory syncytial virus (RSV) is another area where next-generation vaccines are addressing a persistent clinical challenge. It is a leading cause of severe respiratory illness in infants, older adults, and other high-risk populations, with limited effective prevention.10

Next-generation vaccines against RSV are progressing rapidly, with some already in use and others under active investigation, including Moderna’s mRNA-1345, Novavax’s RSV F protein nanoparticle, and Pfizer’s RSVpreF protein subunit vaccine. These approaches mainly aim to elicit robust neutralizing antibody and T-cell responses against a key viral antigen (fusion [F] protein) to reduce hospitalizations and severe disease.10

Advances in genomics and artificial intelligence (AI) are transforming next-generation vaccine development, enabling universal and personalized strategies.

High-throughput sequencing provides detailed profiling of pathogen genomes to identify novel antigens and immunogenic epitopes with high precision. AI algorithms build on this data to guide antigen selection, predict immune responses, and streamline vaccine design and manufacturing.1,11

This process enables a faster, more targeted pathway for vaccine development from discovery to clinical evaluation and improves vaccine specificity and effectiveness. For example, during the COVID-19 pandemic, AI-driven platforms used viral genomic data to rapidly identify potential vaccine targets, significantly accelerating progress and translation into clinical use.1

This integrated approach underpins the development of potential universal vaccines for highly variable pathogens, including next-generation influenza formulations that target conserved viral regions of hemagglutinin (HA) less prone to mutation. Genomic surveillance of circulating strains combined with AI analysis enables identification of these epitopes and prediction of population-level immune responses, offering a more durable alternative to seasonal vaccines.12

Another emerging application of vaccine technology is cancer immunotherapy, where personalized vaccines use patient-specific genomic data and advanced platforms to enhance immune targeting of tumors. AI-driven analysis of tumor genomes enables the identification of unique neoantigens, which can be incorporated into mRNA, DNA, or protein subunit vaccines to stimulate precise T-cell responses against malignant cells.13

Early-phase clinical trials in cancers such as pancreatic cancer have shown promising results, including induction of vaccine-specific T-cell responses, association with delayed recurrence, and feasibility of integration into treatment regimens. Ongoing research is also exploring multi-modal combinations to further improve the efficacy and specificity of these personalized therapeutic strategies.13

Next-generation vaccines represent a major advancement in immunization, offering potential solutions that are widely protective and individually tailored.

Biomedical innovations, together with progress in genomics and AI, are transforming how vaccines are discovered, designed, and evaluated, laying the foundation for more adaptable and resilient protection against disease. As these technologies continue to evolve, they are likely to play a defining role in shaping a new era of immunization.

Olawade, D.B., Teke, J., Fapohunda, O., Weerasinghe, K., Usman, S.O., Ige, A.O., & David-Olawade, A.C. (2024). Leveraging artificial intelligence in vaccine development: A narrative review. Journal of Microbiological Methods, 224, 106998. doi: 10.1016/j.mimet.2024.106998

Gebre, M.S., Brito, L.A., Tostanoski, L.H., Edwards, D.K., Carfi, A., & Barouch, D.H. (2021). Novel approaches for vaccine development. Cell, 184(6):1589-1603. doi: 10.1016/j.cell.2021.02.030

Eslami, M., Fadaee Dowlat, B., Yaghmayee, S., Habibian, A., Keshavarzi, S., Oksenych, V., & Naderian, R. (2025). Next-Generation Vaccine Platforms: Integrating Synthetic Biology, Nanotechnology, and Systems Immunology for Improved Immunogenicity. Vaccines, 13(6):588. doi: 10.3390/vaccines13060588

Khoshnood, S., Ghanavati, R., Shirani, M., Ghahramanpour, H., Sholeh, M., Shariati, A., Sadeghifard, N., & Heidary, M. (2022). Viral vector and nucleic acid vaccines against COVID-19: A narrative review. Frontiers in Microbiology, 13:984536. doi: 10.3389/fmicb.2022.984536

Li, Y., Tenchov, R., Smoot, J., Liu, C., Watkins, S., & Zhou, Q. (2021). A Comprehensive Review of the Global Efforts on COVID-19 Vaccine Development. ACS Central Science, 7(4):512-533. doi: 10.1021/acscentsci.1c00120

Bezbaruah, R., Chavda, V.P., Nongrang, L., Alom, S., Deka, K., Kalita, T., Ali, F., Bhattacharjee, B., & Vora, L. (2022). Nanoparticle-Based Delivery Systems for Vaccines. Vaccines, 10(11):1946. doi: 10.3390/vaccines10111946

Killeen, T., Kermer, V. & Troxler Saxer, R. (2023). mRNA vaccine development during the COVID-19 pandemic: a retrospective review from the perspective of the Swiss affiliate of a global biopharmaceutical company. Journal of Pharmaceutical Policy and Practice, 16, 158. doi: 10.1186/s40545-023-00652-y

Osoro, C.B., Ochodo, E., Kwambai, T.K., Otieno, J.A., Were, L, Sagam C.K., Owino, E.J,, Kariuki, S., Ter Kuile, F.O., & Hill, J. (2024). Policy uptake and implementation of the RTS,S/AS01 malaria vaccine in sub-Saharan African countries: status 2 years following the WHO recommendation. BMJ Global Health, 9(4):e014719. doi: 10.1136/bmjgh-2023-014719

Silk, S.E., Kalinga, W.F., Mtaka, I.M., Lilolime, N.S., Mpina, M., Milando, F., Ahmed, S., Diouf, A., Mkwepu, F., Simon, B., Athumani, T., Rashid, M., Mohammed, L., Lweno, O., Ali, A.M., Nyaulingo, G., Mwalimu, B., Mswata, S., Mwamlima, T.G., ... & Olotu, A.I. (2023). Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults. Med, 4(10):668-686.e7. doi: 10.1016/j.medj.2023.07.003

Kelleher, K., Subramaniam, N., & Drysdale, S.B. (2025). The recent landscape of RSV vaccine research. Therapeutic Advances in Vaccines and Immunotherapy, 13:25151355241310601. doi: 10.1177/25151355241310601

Fitzpatrick, A.H., Rupnik, A., O'Shea, H., Crispie, F., Keaveney, S., & Cotter, P. (2021). High Throughput Sequencing for the Detection and Characterization of RNA Viruses. Frontiers in Microbiology, 12. doi: 10.3389/fmicb.2021.621719

Shah, S.A.W., Palomar, D.P., Barr, I., Poon, L.L.M., Abdul Quadeer, A., & McKay, M.R. (2024). Seasonal antigenic prediction of influenza A H3N2 using machine learning. Nature Communications, 15, 3833. doi: 10.1038/s41467-024-47862-9

Rojas, L. A., Sethna, Z., Soares, K. C., Olcese, C., Pang, N., Patterson, E., Lihm, J., Ceglia, N., Guasp, P., Chu, A., Yu, R., Chandra, A. K., Waters, T., Ruan, J., Amisaki, M., Zebboudj, A., Odgerel, Z., Payne, G., Derhovanessian, E., … & Balachandran, V. P. (2023). Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer. Nature, 618(7952):144–150. doi: 10.1038/s41586-023-06063-y

Last Updated: Oct 9, 2025