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. Author manuscript; available in PMC: 2010 Dec 7.
Published in final edited form as: Nat Biotechnol. 2010 Jun 7;28(6):573–579. doi: 10.1038/nbt.1635

Table 2.

Approaches to viral attenuation for vaccine design

Vaccine
Approach
Advantages Disadvantages Examples
Empirically
attenuated virus
Excellent
immunogenicity, few
doses required
Limited applicability,
reversion to wild type,
breakthrough disease
Measles, mumps, rubella
(MMR); Oral polioirus
vaccine (OPV), Influenza,
Rotavirus, Yellow Fever,
Varicella
Subunit Vaccine Widely applicable, very
safe
Poor immunogenicity,
multiple doses usually
required
Hepatitis B virus, Human
papilloma virus
Viral vectors Good immunogenicity,
delivery of multiple
antigens
Neutralizing antibodies to
vector, possible safety
issues
Many examples
(experimental)
Defective
Viruses
Good immunogenicity,
known mechanism of
attenuation
Limited to inoculation site,
possible safety issues
HSV-1, HSV-2. Influenza
(experimental)
Replication
Fidelity
Strong immunogenicity,
known mechanism of
attenuation, not
susceptible to antigenic
shift/drift
RNA viruses only,
possible reversion to wild
type
Poliovirus (experimental)
Codon
deoptimization
Strong immunogenicity,
no reversion to wild type,
possibly applicable to
many viruses
Possible safety concerns Poliovirus (experimental)
miRNA-
controlled virus
Strong immunogenicity,
known mechanism of
attenuation, prevent
latent infection
Limited to some RNA
viruses
Poliovirus, adenovirus,
coxsackievirus, influenza
(experimental)
ZFN-controlled
virus
Strong immunogenicity,
known mechanism of
attenuation, prevent
latent infection
Limited to non-integrating
DNA viruses