Vaccine platform Preceding cross-reactive immunity CD4+ T cell response CD8+ T cell response Neutralizing antibody response Advantages & disadvantages Ref.
Whole virus vaccines Whole virus vaccines Whole virus vaccines Whole virus vaccines Whole virus vaccines Whole virus vaccines
Live attenuated
Mostly cross-reactive T cells, no cross-reactive B cell
Th1
Potent induction
Potent induction
• Strong B & T cell responses induction following single delivery, award long-term immunity, independent to adjuvants, confer natural antigenicity • Risk for pathogenic reversion, cold chain requirement
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Inactivated
No cross-reactivity
Th1 or Th2 related to adjuvant system
Poor induction
Potent induction
• Safe & stable, no risk of pathogenic reversion, confer natural antigenicity • Poor immunogenicity, need for repeated doses, dependent to adjuvants, costly, inflammatory complications owing to adjuvant
Nucleic acid vaccines Nucleic acid vaccines Nucleic acid vaccines Nucleic acid vaccines Nucleic acid vaccines Nucleic acid vaccines
DNA-based
No cross-reactivity
Th1
Not as potent as some viral vectors
Induction
• Safe & heat stable, low costs, B & T cell responses induction, quick production, award long-term immunity • Relatively weaker immunity, need for repeated doses, induction, risk for insertional mutagenesis, costly, specific delivery vehicle requirement, dependent to adjuvants, unsuitable for RM delivery
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RNA-based
No cross-reactivity
Th1 or Th2 related to adjuvant system
depends on vaccine formulation & adjuvant system
Induction
• B & T cell responses induction, improving antigen presentation, ability of self-adjuvating, quick production, lower probability of adverse effect, no risk of insertional mutagenesis • Need for repeated doses, limited immunogenicity, cold chain requirement, unknown aspects of vaccine delivery & uptake, reluctance to endosomal RNA receptors resulting in faint immune induction, dependent to adjuvants
Replicating vector vaccine Replicating vector vaccine Replicating vector vaccine Replicating vector vaccine Replicating vector vaccine Replicating vector vaccine
VSV
No cross-reactivity
Mainly Th1
Weaker induction than Ad5 & ChAd in single delivery
Induction
• B & T cell responses induction, long-term antigen production, potent immunogenicity with single delivery (VSV) • Costly large-scale production, risk for disease emergence in incompetent hosts, disarm the vector owing to preceding cross-reactive immunity, weaker immunogenicity relative to Ad & limited human safety data (Influenza & measles), suitable for RM delivery (influenza)
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Influenza & measles High probability of cross-reactive B & T cells Mainly Th1 Good induction via RM delivery Induction (impressed by preceding cross-reactive immunity & administration route)
Non-replicating vector vaccines Non-replicating vector vaccines Non-replicating vector vaccines Non-replicating vector vaccines Non-replicating vector vaccines Non-replicating vector vaccines
Ad5
High probability of cross-reactive B & T cells especially in older people
Mainly Th1
Potent induction (impressed by preceding cross-reactive immunity)
Induction (impressed by preceding cross-reactive immunity)
• B & T cell responses induction, long-term antigen production, potent immunogenicity with single delivery (Ad5 & ChAd), suitable for RM delivery, established human safety data • Costly large-scale production, risk for disease emergence in incompetent hosts, disarm the vector owing to preceding cross-reactive immunity, weak immunogenicity & need for repeated booster doses (Ad26)
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Ad26 Medium probability Mainly Th1 Medium induction (impressed by preceding cross-reactive immunity) Induction (impressed by preceding cross-reactive immunity)
ChAd Almost no cross-reactivity Mainly Th1 Potent induction Induction
Subunit vaccines Subunit vaccines Subunit vaccines Subunit vaccines Subunit vaccines Subunit vaccines
Protein-based
No cross-reactivity
Th1 or Th2 related to adjuvant system
Poor induction
Potent induction
• Safe with no risk of infection, selecting highly immunogenic antigens, strong neutralizing antibody induction • weaker induction of T cell response, decreased immune response over time, need for repeated booster doses, costly, dependent to adjuvants, unsuitable for RM delivery
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Virus-like particle (VLP) vaccines Virus-like particle (VLP) vaccines Virus-like particle (VLP) vaccines Virus-like particle (VLP) vaccines Virus-like particle (VLP) vaccines Virus-like particle (VLP) vaccines
VLP
No cross-reactivity
Th1 or Th2 related to adjuvant system
Poor induction
Potent induction
• Safe with no risk of infection, strong neutralizing antibody induction, ability of self-adjuvating, cross-linking of surface BCRs by condensed & repetitive antigen presentation, established platform for human vaccines • Providing high yield, stable, immunogenic VLP with suitable quality is challenging, risk for a host cell-derived component, need for repeated booster doses
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