Vaccination-induced herd immunity: Successes and challenges

The World Health Organization estimates that global vaccination programs save 2 to 3 million lives per year by priming the immune system to protect against pathogenic threats that pose significant global health and economic burdens (Fig 1, A).1 In addition to individual protection, vaccination programs also rely on population or “herd” immunity: immunization of large portions of the population to protect the unvaccinated, immunocompromised, and immunologically naive by reducing the number of susceptible hosts to a level less than the threshold needed for transmission. [...]immunization of greater than 80% of the global population against smallpox virus reduced transmission rates to uninfected subjects to a point low enough to achieve eradication of the virus.1 Similarly, although the extent of coverage needed is pathogen specific, poliovirus is now targeted for eradication, with only Pakistan, Afghanistan, and Nigeria documenting endemic viral infections.1 Despite the success of select vaccination programs (Fig 1, B),2 societal and biological factors, including the inability of population groups to generate protective immunity in response to vaccination, are a challenge for achieving herd immunity. Infection with one serotype induces production of both cross-reactive and serotype-specific neutralizing antibodies during initial infection.7,8 On infection with a second serotype, the original memory immune response is stimulated preferentially. Because of antigenic differences between the primary and secondary viruses, pre-existing antibody is unable to effectively neutralize the second virus, allowing immune evasion through immune imprinting (original antigenic sin/antigenic seniority).7,8 Importantly, depending on the level and neutralization capacity of the cross-reactive pre-existing antibodies, a secondary infection can cause severe disease.8 Similarly, the immune system preferentially recalls memory antibody responses to the earliest infecting strains of influenza A virus and norovirus and shows weaker consecutive responses to infection with subsequent serotypes, respectively.6,8,9 Because the herd is composed of subjects from many different age groups and pandemic influenza and norovirus strains change over time, effective vaccine development that induces broad protection is highly complicated by age and pre-exposure history.