Despite remarkable success of immunization programmes on a global perspective, vaccines are neither 100% efficacious nor 100% effective. Therefore, vaccination failure, i.e. occurrence of a specific disease in an individual despite previous vaccination, may occur. Vaccination failure may be due to actual vaccine failure or failure to vaccinate appropriately.
A. Vaccine failure
(1) Vaccine-related(host-related):
- (a) immunodeficiency (leading to suboptimal or even absent immune response after vaccination);
- (b) age-related maturation and senescence of immune responsiveness;
- (c) insufficient or suboptimal immune response (other than a defined immunodeficiency) to one or more antigenic vaccine components or vaccine strains or serotypes; this may or may not be measurable
by standard laboratory tests such as serum antibody tests; - (d) interference due to other infectious agents (e.g. wild type enterovirus infection causing interference with the immune response to oral poliomyelitis vaccine (OPV));
- (e) waning immunity;
- (f) suboptimal health status (e.g. underlying disease, nutrition);
- (g) immunological interference (e.g. maternal antibodies, administration of immunoglobulins);
- (h) pre-existing infection with pathogen targeted by the vaccine (e.g. with specific HPV genotypes) or immunization during incubation period (after exposure to pathogen);
- (i) immunosuppressive therapy.
(2) Vaccine-related:
- (a) vaccine is not 100% efficacious against included antigens;
- (b) incomplete coverage of strains, serotypes, genotypes, antigenic variants or escape mutants that can cause a vaccine-preventable disease;
- (c) antigenic interference or other vaccine-vaccine interactions in case of co-administered vaccines;
- (d) manufacturing-related (e.g. batch variations, quality defect).
B. Failure to vaccinate
(3) Usage issues:
- (a) administration error (wrong or suboptimal route, inadequate dose, incorrect diluent);
- (b) vaccination series incomplete, non-compliance with recommended schedule, including lack of recommended booster vaccination(s) (“failure to vaccinate” rather than “vaccination failure”);
- (c) storage-related (e.g. cold chain);
- (d) vaccine beyond expiry date when used.
(4) Immunization programme-related issues:
- (a) suboptimal recommendations regarding number and time points of primary and/or booster vaccinations;
- (b) shortage of vaccine leading to no or incomplete vaccination.
Confirmed clinical vaccine failure
The occurrence of the specific vaccine-preventable disease in a person who is appropriately and fully vaccinated taking into account the incubation period and the normal delay for the protection to be acquired as a result of immunization.
Suspected clinical vaccine failure
Suspected vaccine failure is defined as the occurrence of disease in an appropriately and fully vaccinated person, but the disease is not confirmed to be the specific vaccine-preventable disease, e.g. invasive pneumococcal disease of unknown serotype in a fully vaccinated person.
Confirmed immunological vaccine failure
In addition to clinical vaccine failure, there is the possibility of immunological vaccine failure, not necessarily associated with a clinical manifestation of the vaccine-preventable disease. Immunological failure is defined as failure of the vaccine to develop the accepted marker of protective immune response after being fully and appropriately vaccinated.
Reference: Report of CIOMS/WHO Working Group on Vaccine Pharmacovigilance – Definition and Application of Terms for Vaccine Pharmacovigilance
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