Table 2 Summary of platforms used for developing and manufacturing vaccines for COVID-19

Inactivated virus

Heat/radiation/chemical inactivation of replicated viruses in cell lines

Well established technology, contains whole genome and proteins of virus for immunogenicity, no chance of infection

Slow production in cell lines, adverse effects due to adjuvant or virus components, BCL3 facilities, high quality control, different cell lines and related issues, several boosting injections for longer immunity

[138, 139]

Live attenuated

Weakened modified replicated viruses in cell lines

Well established technology, strong long-term immunity, contains whole genome and proteins of virus for immunogenicity

Slow production in cell lines, BCL3 facilities, Risk of infection in individuals, possible pathogen polymorphism inside host, safety concerns for risk groups

[138, 139]

Protein subunits

Components of purified viral antigens produced by recombinant technology

Safe with less adverse effects, no BCL3 facilities for virus replication, non-infection, strong humoral response

Limited selection of Ag and partial protection, Ag adaptation in the pathogen for better fitness in host, need adjuvant for better immunisation, poor induction of cellular responses, no cellular immune response

[138, 139]

Virus like particles (VLP)

Complex of several viral proteins that have ability to self-assemble when recombinantly expressed in various bacterial or yeast platforms without having the viral genome produced

Non-infection, strong humoral responses, do not need adjuvant, optimal size to be absorbed by antigen presenting cells (APC)

Complex manufacturing process, stability issues, impurities during production, side effects of expression systems

[140, 141]

Viral vector (replicating or non-replicating)

Integration of target genes into another harmless viral genomes (mostly adenoviruses) as a carrier and then the target gene is expressed by the host cells

Non-infection induction of T and B cell immune response, long term gene expression

Potential risk of vector and related adverse effects, reduced efficacy in case of pre-existing vector immunity, induction of vector immunity rather than target virus, time and cost due to cell line-based production

[142, 143]

DNA-based

Integration of target gene into plasmid as a carrier and then the target gene is expressed by the host cells

Induction of T and B cell immune response, non-infectious, no BCL3 facilities for virus replication rapid, egg and cell line free, cost and time effective, stable vaccine for transportation

Potential integration into human genome, poor immunogenicity in human, not enough data for safety and efficacy

[138, 139]

Conventional mRNA (non-replicating mRNA, NRM)

Synthetic mRNA (flanked by 5′ and 3′ untranslated regions (UTRs), a 5′-cap structure and a 3′-poly-(A) tail) of target gene encapsulated in synthetic lipid or polymer carrier as a carrier and then the target gene is expressed by the host cells

Rapid scale production, cell line free, no BCL3 facilities, egg and cell line free, strong T cell response, non-infection

Not enough data for safety and efficacy, higher dose of RNA compared to SAM, possible degradation of mRNA in the host cells leading decline in vaccine potency

[127, 144]

Replicon (self-replicating mRNA, SAM)

Auto-replicative activity by adding a large open reading frame for four non-structural proteins and sub-genomic promoter at the 5′ end and encapsulated in the lipid as a carrier and then the target gene can be amplified by itself and then expressed by the host cells

Rapid scale production, cell line free, no need for BCL3 facilities, egg and cell line free, lower dose of RNA compares to RNM due to self-replicative properties, induction of T and B cell immune response

Not enough data for safety and efficacy, larger sequence size and more complicated design compared to SAM since it needs replicons for self-amplifying activity, possible degradation of mRNA in the host cells leading decline in vaccine potency

[127, 144]

Plant-based (edible vaccines)

Integration of antigen gene in the genome of

Large scale production, no adverse effects due to injection, time and cost effective for large production, no adjuvants or harmful components, no need for cold chain transportation and delivery, not need high end and BCL3 facilities for production

Consistency of dosage in plants and individuals, vaccine dosage might be variable due to the size of plants, instability during food preparation, not convenient for infants

[132, 133]