Personal ViewNew approaches to the assessment of vaccine herd protection in clinical trials
Introduction
Herd protection is the protective effect of a vaccine in a population that exceeds the effect expected on the basis of the known protective efficacy within individuals and the level of vaccine coverage.1 Herd protection has been suggested for a diverse array of vaccines used in public health practice.2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Interest in herd protective effects of newly developed vaccines has increased for several reasons. First, recently developed and licensed vaccines, such as those against rotavirus, pneumococcus, and human papillomavirus, are substantially more expensive than are traditional childhood vaccines.13, 14, 15, 16, 17 In some cases, the cost-effectiveness profile of such vaccines becomes favourable only if herd protective effects are considered.18 Second, some new generation vaccines, such as orally administered vaccines against cholera, confer moderate degrees of protective efficacy within individuals, and the demonstration of herd protective effects might establish whether the use of such vaccines in populations will be sufficient for disease control.19 Third, the herd protective effects of vaccines could change the epidemiology and ecology of microbial pathogens, sometimes with deleterious consequences such as shifting the average age of infection by a pathogen or helping to set the stage for replacement of the targeted pathogen by a related pathogen.20, 21, 22
Evidence about a vaccine's herd protective effects generated by clinical studies of a vaccine done at an early stage, even before licensure, would benefit policy decisions about deployment of a vaccine. Here we discuss the notion of vaccine herd protection, ways to measure vaccine herd protection both before and after licensure, and the relative strengths of the different evaluative approaches.
Section snippets
Vaccine herd protection
Vaccine-induced herd effects include vaccine herd immunity and vaccine herd protection, and these two terms are often used interchangeably. We use the term vaccine herd immunity to describe the protection of non-vaccinated people exposed to live vaccine organisms transmitted by shedding of these organisms by vaccinees, leading to a protective immune response,23 as happens with live oral polio vaccine.24 Herd immunity, used in this way, applies only to live vaccines and does not depend on
Traditional assessments after vaccine licensure
Traditionally, the herd protective effects of vaccines have been studied only after their licensure and use in public health practice. Both concurrent and non-concurrent study designs have been used. An example of a concurrent study design was a study of the incidence of measles in non-vaccinated children residing in different regions of Milwaukee, WI, USA.28 In this study, the investigators showed that the incidence of measles among non-vaccinated children who were concurrently followed up was
New approaches
Small clinical trials are often done before licensure to assess whether a vaccine reduces mucosal colonisation by the target pathogen among vaccinees, reasoning that prevention of colonisation by vaccination might translate into vaccine herd protection. Both pneumococcal polysaccharide-protein and Haemophilus influenzae type b polysaccharide-protein conjugate vaccines are known to provide protection to vaccinees against nasopharyngeal colonisation with vaccine-targeted organisms, and this
Conclusions
Data on herd protection are important in the assessment of the public health effect and cost-effectiveness of many vaccines. Studies of vaccine herd protection are often needed to inform policy decisions about vaccine introduction. Previously, assessments of vaccine herd protection had typically been deferred until a vaccine had been used in practice. For some vaccines, especially those for which introduction into practice might be impeded by cost, less than optimum direct protection, or other
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Estimating sibling spillover effects with unobserved confounding using gain-scores
2022, Annals of EpidemiologyEvaluation of protection by COVID-19 vaccines after deployment in low and lower-middle income countries
2022, eClinicalMedicineCitation Excerpt :Notably, no field evaluations of vaccine impact in L/MICs were identified during the time frame for our literature search. Application of Geographical Information Systems (GIS) to epidemiological studies offers another approach to measuring vaccine herd protection and impact, which, although not yet used for COVID-19 vaccines, has been used for field measurement of herd protection by OCVs, as cited earlier.77,78 With this approach vaccine herd protection and impact can be estimated by evaluating the occurrence of COVID-19 in each individual in the population in relation to the vaccine coverage of a cluster of surrounding persons demarcated by GIS.
Effectiveness of a killed whole-cell oral cholera vaccine in Bangladesh: further follow-up of a cluster-randomised trial
2021, The Lancet Infectious Diseases