Table 1.
Summary of vaccine-resistance case studies in main text
| Issues | Hepatitis B virus | S. pneumoniae | B. pertussis | Y. ruckeri | Avian metapneumovirus | Marek’s disease virus |
| Reason vaccine resistance was first suspected | Variation in key antigens | Variation in key antigens | Outbreaks in vaccinated populations | Outbreaks in vaccinated populations | Outbreaks in vaccinated populations | Outbreaks in vaccinated populations |
| Evidence of resistance | ||||||
| Direct experiments | Negative* | Not done | Positive* | Mixed | Positive | Positive |
| Molecular epidemiology | Positive | Positive | Positive | Not done | Not done | Not done |
| Mechanistic plausibility | Positive | Positive | Positive | Positive | Positive | Positive |
| Expert opinion | Positive | Positive | Positive | Positive | Positive | Positive |
| Putative route of resistance | Immune evasion | Immune evasion | Immune suppression and immune evasion | Loss of immune stimulation | Immune evasion | ?† |
| Impact of vaccine resistance on disease | ||||||
| Population level | Extremely small | Slight increase | ?‡ | ?§ | ?§ | Large increase¶ |
| Vaccinated host | Rare disease | Slight increase | ?‡ | Mixed evidence | Increase | Mild to severe |
| Unvaccinated host | ?# | Slight decrease | ?‖ | ? | No change | Very severe |
| Prompted development of vaccination strategies to combat resistance? | No | Yes | Unclear** | Yes | No | Yes |
Animals models, not natural hosts. For HBV, the putative vaccine-resistant strain was unable to infect vaccinated chimpanzees, even though it was able to replicate in unvaccinated animals. For B. pertussis, there was unambiguous evidence for prn−; ptxP3 evidence was mixed (main text).
Resistance correlates with virulence in unprotected hosts.
Debate over the degree to which resurgence in cases (Fig. 2) is attributable to vaccine resistance.
Despite lack of data, disease is presumably reduced given that vaccination is still widely used in the industry.
Vaccine-resistant isolates reduce survival and increase condemnation rates in flocks vaccinated with first-generation vaccines.
Vaccine-resistant isolates may have reduced pathogenicity due to fitness costs of resistance, but not obviously seen in the animal model (main text).
Some vaccine-resistant isolates may have increased virulence in unvaccinated hosts (main text).
New vaccines are in development but it is not clear that these are being developed to combat vaccine-resistant pathogen strains rather than, for example, waning immunity.