Biological challenges to effective vaccines in the developing world

Abstract

The reason for holding a meeting to discuss biological challenges to vaccines is simple: not all vaccines work equally well in all settings. This special issue reviews the performance of vaccines in challenging environments, summarizes current thinking on the reasons why vaccines underperform and considers what approaches are necessary to understand the heterogeneity in responses and to improve vaccine immunogenicity and efficacy.

Keywords: immunization; immunology; infectious disease; vaccine; vaccinology.

Figure 1.

Limited or variable effectiveness of existing vaccines leaves children at risk of infection. (a) The number of children born each year who are vaccinated with commonly used vaccines based on country-specific estimates of immunization coverage and numbers of births for 2013 [2,3]. Coverage of the birth cohort is shown on the right-hand axis. (b) Estimated individual effectiveness of each vaccine presented as a global average based on country-specific estimates weighted by the number of children immunized in each country. (c) The number of children born each year who are vaccinated but remain unprotected based on the estimates in A and B at current levels of coverage or if coverage with Haemophilus influenzae type B (Hib), pneumococcal vaccine (PCV) and oral rotavirus vaccine (ORV) reached at least 80% in each country. Children who are incompletely vaccinated are not included in these estimates. Country-specific vaccine effectiveness estimates are based on published data for BCG vaccination against pulmonary tuberculosis (assuming 70% for more than 40° latitude and 30% for 0–40° [4]), diphtheria toxoid [5], tetanus toxoid [6,7], acellular or whole-cell pertussis vaccines using predominant usage patterns by WHO region [8], hepatitis B vaccine (ignoring the effect of limited coverage birth dose administration [9]), Hib vaccine against meningitis [10], single dose measles vaccine [11], pneumococcal vaccine against invasive pneumococcal disease caused by vaccine serotypes (mainly based on PCV9 or PCV7 [12]), trivalent oral poliovirus vaccine [13,14], oral rotavirus vaccine [15] and yellow fever vaccine [16]. (Online version in colour.)

Figure 2.

A new paradigm for vaccine research that starts with analysis of variation in the human immune response to vaccination. Adapted from [34]. (Online version in colour.)