Vaccines and immunological therapies have transformed healthcare by preventing infectious diseases and strengthening immune protection. From early polio vaccines to modern mRNA-based approaches, progress in this field has depended heavily on reliable cell models. Immortalised cell lines provide the scalability, reproducibility, and accessibility required to test immune responses, evaluate viral replication, and produce vaccine components. By mimicking different aspects of human physiology, they allow researchers to bridge the gap between laboratory discovery and clinical translation. The following sections explore ten cell lines and their crucial role in vaccine development and immunology.
HeLa Cells and Early Vaccine Breakthroughs
The history ofHeLa cells is closely tied to vaccine development. Derived from cervical carcinoma, these immortalised cells were used extensively in the 1950s to grow poliovirus, enabling mass testing of the first polio vaccines. Their rapid growth and robustness made them one of the earliest systems for large-scale viral replication. Beyond polio, HeLa cells have contributed to influenza vaccine studies, measles virus replication, and adenovirus biology. In immunology, they are frequently used to test cytotoxic responses, offering insights into how immune cells recognise and destroy virus-infected targets. Although their genomic instability limits their direct comparability to normal tissues, their contribution to vaccine history remains unparalleled.
HEK293 and Viral Vector Vaccines
HEK293 cells are perhaps the most prominent modern cell line in vaccine research. Their high transfection efficiency and adaptability make them ideal for producing viral vectors, which are critical components of gene-based and viral-vector vaccines. HEK293 cells have been widely used in the development of adenovirus-based vaccines, including those deployed against COVID-19. They are also indispensable for producing lentiviral and retroviral vectors used in gene immunotherapy. In immunology, HEK293 allows researchers to express receptors and antigens for vaccine evaluation, linking genetic design to functional immune responses. Their versatility ensures that they remain central to future vaccine platforms, especially those based on engineered viruses.
CHO Cells and Biomanufactured Vaccine Proteins
CHO cells are central to industrial-scale vaccine production. As the dominant platform for manufacturing recombinant proteins, they provide the infrastructure for producing vaccine antigens and adjuvant proteins in large quantities. Their ability to generate human-compatible glycosylation patterns ensures that vaccine proteins maintain correct structure and immunogenicity. CHO cells are used to produce viral subunit vaccines, monoclonal antibodies for passive immunisation, and adjuvant proteins that enhance immune responses. Their scalability in bioreactors makes them the gold standard for bringing laboratory-developed vaccines to clinical distribution, highlighting their dual role in research and production.
SH-SY5Y and Neurotropic Vaccine Research
Neurotropic viruses such as poliovirus, rabies, and flaviviruses present unique challenges in vaccine design because they target neuronal systems. SH-SY5Y cells, derived from neuroblastoma, provide a model for investigating how these viruses interact with neuronal pathways. They can be differentiated into neuron-like cells, making them suitable for studying viral entry, replication, and host response in nervous tissue contexts. Researchers have used SH-SY5Y to explore rabies vaccine mechanisms, model Zika virus neurotropism, and evaluate the neuronal toxicity of vaccine adjuvants. Although tumour-derived, their adaptability makes them one of the few reproducible neuronal models available for immunology and virology.
MCF7 and Hormone-Related Immune Modulation
The MCF7 breast cancer line retains oestrogen receptor activity, giving it relevance in immunology where hormones influence immune responses. Vaccinology increasingly recognises sex-specific differences in immunity, and MCF7 helps clarify the molecular basis of these differences. Researchers use MCF7 to investigate how oestrogen modulates vaccine-induced immunity, including antibody production and T-cell responses. They are also applied in testing the immunological impact of endocrine-disrupting chemicals, which may weaken or skew vaccine responses. By linking hormonal pathways with immune regulation, MCF7 contributes to a more personalised understanding of vaccine efficacy across different populations.
THP1 and Immune System Modelling
The monocytic THP1 line is a cornerstone of immunological research. These cells can differentiate into macrophage-like phenotypes, making them ideal for studying innate immune responses. In vaccine research, THP1 cells are used to model antigen presentation, cytokine release, and immune activation following exposure to vaccine components. They are also employed in immunotoxicology, where researchers test whether vaccine adjuvants overstimulate or suppress innate immunity. By providing a reproducible platform for innate immune studies, THP1 cells are invaluable for bridging vaccine development with immunological safety assessments.
A2780 and Vaccine Development in Oncology
Cancer vaccines are an emerging area of immunology, andA2780 ovarian carcinoma cells provide a model for testing therapeutic cancer vaccines. Their responsiveness to DNA-damaging agents and their defined tumour antigens make them useful for exploring oncovirus-related immunology and vaccine design. A2780 cells have been employed to test oncolytic virus vaccines that target ovarian tumours, as well as immune checkpoint inhibitors combined with vaccination strategies. By linking tumour immunology with vaccine design, A2780 cells illustrate how immunisation concepts extend beyond infectious disease to cancer therapy.
HL-60 and Haematopoietic Immunology
The promyelocytic HL-60 line, capable of differentiating into granulocytes or monocytes, provides an excellent model for studying immune cell development. In vaccine immunology, HL-60 cells help clarify how vaccine adjuvants and viral components affect blood cell maturation. They are also applied in testing myelotoxicity of vaccines and drugs, ensuring that immunisation strategies do not impair haematopoietic regeneration. HL-60 research underscores the importance of haematological safety in vaccine development, particularly in populations with weakened bone marrow reserves.
Caco-2 and Mucosal Vaccine Studies
Mucosal immunity is critical for protecting against gastrointestinal pathogens, and Caco-2 cells provide a reproducible model for studying vaccine interactions at the intestinal barrier. When cultured, they differentiate into enterocyte-like cells, replicating epithelial functions of the gut. They are widely used to test oral vaccine formulations, assess mucosal adjuvants, and evaluate how dietary factors influence vaccine uptake. Caco-2 studies also extend to the role of microbiota–vaccine interactions, which are increasingly recognised as modulators of immune efficacy. By representing the frontline of mucosal defence, Caco-2 cells support research into next-generation vaccines that target gut immunity.
HepG2 and Hepatitis Vaccine Development
TheHepG2 hepatocellular carcinoma line is among the most important systems for hepatitis vaccine research. Retaining key hepatic functions, HepG2 cells allow researchers to study hepatitis B and C virus biology, test antiviral responses, and evaluate vaccine-induced immunity. They are also applied in exploring hepatotoxicity of vaccine adjuvants and identifying biomarkers of liver-specific immune responses. Beyond hepatitis, HepG2 provides a platform for understanding how vaccines influence metabolic processes in the liver, ensuring both efficacy and safety. Their stability and reproducibility make them indispensable for vaccine-related hepatology research.
Conclusion
Immortalised cell lines have become pillars of vaccine development and immunology, providing scalable and reproducible systems for studying immune responses, viral replication, and vaccine safety. HeLa enabled early polio vaccine breakthroughs, HEK293 powers viral vector vaccines, and CHO supports large-scale antigen production. SH-SY5Y contributes to neurotropic vaccine studies, MCF7 links hormones to immune responses, and THP1 models innate immunity. A2780 brings immunology into oncology vaccines, HL-60 clarifies haematological safety, Caco-2 advances mucosal vaccine research, and HepG2 enables hepatitis vaccine development. Together, these lines ensure that vaccine innovation continues to evolve, offering protection against both infectious and non-infectious diseases.
