| Vaccine Platform | Description | Advantages | Disadvantages |
| Virus-like Particles (VLPs) | Structurally mimic the native virus by presenting key antigens (e.g., spike protein) in a highly organized, repetitive array, but lack any viral genetic material, making them non-infectious | Induce strong B-cell and T-cell responses Highly immunogenic due to dense antigen display No risk of replication or infection Good safety profile Often stable for storage | Complex and costly manufacturing Scalability challenges Often require adjuvants and booster doses Limited cross-protection without multivalent design |
| Protein Subunit | Use isolated viral proteins (typically the spike protein or receptor binding domain) as the antigen to elicit an immune response | Good safety profile; no live components Established manufacturing processes Well-tolerated with few severe side effects Flexible for targeting specific viral strains or variants | Lower immunogenicity alone; almost always needs adjuvants Typically requires multiple doses Potential for incomplete immune response without correct folding/glycosylation of proteins |
| Nanoparticle | Deliver viral antigens via synthetic particles, such as lipid nanoparticles, polymeric particles, or inorganic (e.g., ferritin-based) nanoparticles; can multivalently display antigens | Enhances delivery to antigen-presenting cells Stabilizes antigens structurally Can amplify immune responses via particle size/shape Flexibility to co-deliver adjuvants | Manufacturing complexity (consistency, scale-up) Potential unknown long-term effects of some nanoparticle materials May require specialized storage conditions |
| Viral Vector | Use a genetically modified virus (e.g., adenovirus, measles virus) to deliver genes encoding coronavirus proteins to host cells, which then express the viral antigen internally. Can be non-replicating or replicating | Induces both humoral and cellular immune responses Single-dose protection possible Thermal stability better than mRNA vaccines Established platform for rapid updates | Pre-existing immunity to the viral vector can reduce vaccine efficacy Rare risk of vector-related adverse events (e.g., thrombosis for adenovirus vectors) Complex regulatory approval pathways |
| Inactivated Virus | The whole virus is grown in culture and chemically or heat-inactivated to prevent replication, but retains antigenic structure to elicit an immune response. | Well-established platform used in many licensed vaccines Induces broad antibody responses to multiple viral antigens Lower risk of adverse events related to replication than attenuated virus | May not induce strong T-cell responses Typically needs multiple doses and adjuvants Potential for antibody-dependent enhancement (ADE) if neutralization is suboptimal |
| Nucleic Acid/Nanoparticle (mRNA-LNP vaccines) | mRNA encoding viral antigens (e.g., spike protein epitopes) is encapsulated in lipid nanoparticles to protect it and facilitate entry into host cells, where the antigen is produced in situ. | Rapid design and production capabilities Strong B-cell and CD8+ T-cell responses No risk of infection or genome integration Highly adaptable to emerging variants | Requires ultracold storage (-20°C to -80°C) for some formulations Higher rates of transient reactogenicity (e.g., fever, myalgia) Lipid nanoparticle components can cause inflammation or rare allergic reactions |
| Nucleic Acid/Plasmid (DNA vaccines) | Plasmid DNA containing the gene for a viral antigen is delivered to host cells, often via electroporation, where it is transcribed into mRNA and translated into viral proteins. | Stable at room temperature or under refrigeration Inexpensive and scalable production Safe; no live components or replication risk No need for cold chain at mRNA levels | Generally weaker immunogenicity in humans compared to mRNA Delivery often requires electroporation devices, limiting easy administration Potential concerns about integration into host DNA, though extremely rare |
| Live-attenuated Virus | A weakened version of the virus that can replicate at low levels without causing disease, stimulating a natural, broad immune response involving both arms of the immune system | Mimics natural infection; very strong and durable immune responses Typically induces lifelong immunity after 1–2 doses May provide mucosal immunity if given intranasally. | Risk of reversion to virulence, especially in immunocompromised people Requires careful attenuation and safety testing Complex manufacturing under tight biosafety controls. Less suitable for older adults or immunosuppressed populations. |
References
Acosta-Coley I, Cervantes-Ceballos L, Tejeda-Benítez L. et al. Vaccines platforms and COVID-19: what you need to know. Trop Dis Travel Med Vaccines 2002;8(20). https://doi.org/10.1186/s40794-022-00176-4
Baghban R, Ghasemian A, Mahmoodi S. Nucleic acid-based vaccine platforms against the coronavirus disease 19 (COVID-19). Arch Microbiol 2023;205(150). https://doi.org/10.1007/s00203-023-03480-5
Ho NT, Hughes SG, Sekulovich R et al. A randomized trial comparing safety, immunogenicity and efficacy of self-amplifying mRNA and adenovirus-vector COVID-19 vaccines. npj Vaccines 2024;9(233). https://doi.org/10.1038/s41541-024-01017-5
Kudlay D, Svistunov A, Satyshev O. COVID-19 vaccines: an updated overview of different platforms. Bioengineering (Basel) 2022 Nov 19;9(11):714. http://doi.org/10.3390/bioengineering9110714
Vivek P. Chavda, Lalitkumar K. Vora, Vasso Apostolopoulos. Developments in Immunology, Advanced Vaccination Technologies for Infectious and Chronic Diseases. Academic Press (2024), ISBN 9780443185649. https://doi.org/10.1016/B978-0-443-18564-9.01001-8