Abstract
BackgroundIn the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.MethodologyWe report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.Principal FindingsBoth in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.ConclusionsIt is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.Trial registrationClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287
Highlights
Understanding vaccine safety requires a comprehensive assessment of all events that occur after the administration of a vaccine
In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported
We report and discuss the results from five clinical trials where the absolute neutrophil counts (ANC) were evaluated before and after vaccination
Summary
Understanding vaccine safety requires a comprehensive assessment of all events that occur after the administration of a vaccine. A previous example where an adverse event, identified by an abnormality in a laboratory parameter, has been associated with administration of a vaccine, is idiopathic thrombocytopenic purpura, linked to the administration of measles-containing vaccines. The identification of this association required several retrospective observational studies analyzing data from millions of young children over the past two decades [1, 2]. A clear understanding of the potential risks early on will allow for more comprehensive assessments prospectively following licensure and will provide more information to be availed to the public increasing trust in the vaccination program. It is important to evaluate how these trials should be planned not to miss potentially important safety signals, and to understand the implications and the clinical relevance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
