Safety of Co-Administration Versus Separate Administration of the Same Vaccines in Children: A Systematic Literature Review.

Jorgen Bauwens,Nino Künzli,Annina Reusser,Luis-Henri Saenz,Jan Bonhoeffer

doi:10.3390/vaccines8010012

Abstract

The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and Haemophilus influenzae type b conjugate (DTaP-HepB-IPV/Hib) vaccine, measles, mumps, and rubella (MMR) vaccine, and pneumococcal conjugate 7-valent (PCV7) or 13-valent (PCV13) vaccines. Of this, 16% (n = 8) of the studies reported significantly more adverse events following immunization (AEFI) while in 10% (n = 5) significantly fewer adverse events were found in the co-administration groups. Statistically significant differences between co-administration and separate administration were found for 16 adverse events, for 11 different vaccine co-administrations. In general, studies briefly described safety and one-third of studies lacked any statistical assessment of AEFI. Overall, the evidence on the safety of vaccine co-administrations compared to separate vaccine administrations is inconclusive and there is a paucity of large post-licensure studies addressing this issue.

Highlights

With new vaccines becoming available and added to pediatric immunization schedules, these schedules become increasingly crowded [1,2]
Evidence about no increased risk of adverse events when co-administering vaccines compared to separate vaccine administration is indispensable to improve immunization rates
Opposition to vaccination and under-vaccination are crucial threats to herd immunity [50], which can be addressed by proving the safety of vaccine co-administration

Summary

Introduction

With new vaccines becoming available and added to pediatric immunization schedules, these schedules become increasingly crowded [1,2]. Since co-administering vaccines may facilitate the introduction of new vaccines to immunization schedules and positively affect coverage rates [3], a growing number of vaccines is likely to be co-administered in the future. Uncertainty about the safety of co-administered vaccines can contribute to vaccine hesitancy in parents [4,5]. This highlights the need for assessing the safety of co-administered vaccines. Immunization schedules are typically designed based on evidence of efficacy and safety from clinical trials. Both the number and types of vaccines co-administered in routine

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