Table 3.

Merits and demerits of various vaccine approaches

Type of vaccine	Target antigen	Merits	Demerits
Live attenuated	Whole virus	•Induction of strong and long-lasting B and T cell immune responses [55], [56] •Confers lifelong immunity within 2 doses [57] •Intranasal administration provides local mucosal immunity through secretion of IgA [57] •Inexpensive and easy to produce [43], [56], [57] •Less adverse effects [43]	•Requires cold chain [56] •Genetic reversion increases the risk of infection especially in immunocompromised individuals [42], [55] •Not suitable to all age groups [43] •May require Biosafety Level-3 (BSL-3) facility [43]
Inactivated whole virus	Whole virus	•Infectivity destroyed without compromising the immunogenicity [55] •Safe vaccines as no live virus is present and cannot cause disease [55], [56] •Produces high titres of neutralizing antibodies [43] •Stable vaccines [55] •Does not require cold chain and can be freeze dried [56] •Easy to prepare [43]	•Produces a weaker immune response and hence adjuvants are required to provide an effective immune response [57] •Risk of vaccine-enhanced disease and hypersensitivity reactions [42], [43], [56] •Requires live virus and facility to grow large amounts [42]
Subunit	S protein	•Safe as viral particles cannot cause infection [55], [56] •Selected viral particles are highly immunogenic and induce strong neutralizing antibodies [55] •Can induce cellular and humoral immune responses [43] •Cost-effective production [57]	•Weaker immune response over time [55] •Lower immunogenicity [43] •Requires repeated doses and adjuvants [43]
VLPs	S protein	•Lacks genetic material and hence non-infectious in nature [57] •Highly immunogenic [58] •Stimulates robust cellular and humoral immune responses due to their highly repetitive display of antigenic epitopes [58] •Possess excellent adjuvant properties [59]	•Challenges - optimal quality, stability, and good immunogenicity at high yield [55]
Viral vector (both replicating and non-replicating)	S protein	•Long-term gene expression [55] •High safety [43], [60], [61] •Induces strong cellular and humoral responses [43], [60], [61]	•Risk of infection [60] •Risk for chromosomal integration and oncogenesis [[60], [61]] •Pre-existing immunity to vectors [[60], [61]] •Inflammatory adverse events [[60], [61]]
DNA	S protein	•Rapid development and production [61] •Safe as it cannot cause disease and no risk of infection [55], [56], [61] •Induces both humoral and cellular responses [55], [60], [61] •Inexpensive [55], [57] •Long-term stability [60], [61]	•No real-world experience till date [60] •Requires specialized delivery tools [[43], [60]] •Poor immune response [[43], [61]] •Repeated doses may cause toxicity [[43], [61]] •Risk of genetic integration [[60], [61]]
RNA	S protein	•Rapid development and production [61] •No risk of genetic integration [61] •Induces strong humoral and cellular responses [60], [61] •Options for multivalent formulations [60], [61] •High safety as it cannot cause disease [56], [61] •Direct delivery to the cytosol enhances antigen expression [55]	•Requires cold chain for stability and longevity [60] •Lack of interaction with endosomal RNA receptors may weaken immunostimulation [55] •Inflammatory / Adverse reactions possibility [[60], [61]] •High cost [61] •Booster doses required for long-lasting and robust immunity [60]