Safety, Immunogenicity, Efficacy and Effectiveness of Inactivated Influenza Vaccines in Healthy Pregnant Women and Children Under 5 Years: An Evidence-Based Clinical Review

Abstract

Annual influenza vaccination is often recommended for pregnant women and young children to reduce the risk of severe influenza. However, most studies investigating the safety, immunogenicity, and efficacy or effectiveness of influenza vaccines are conducted in healthy adults. In this evidence-based clinical review, we provide an update on the safety profile, immunogenicity, and efficacy/effectiveness of inactivated influenza vaccines (IIVs) in healthy pregnant women and children <5 years old. Six electronic databases were searched until May 27, 2021. We identified 3,731 articles, of which 93 met the eligibility criteria and were included. The IIVs were generally well tolerated in pregnant women and young children, with low frequencies of adverse events following IIV administration; however, continuous vaccine safety monitoring systems are necessary to detect rare adverse events. IIVs generated good antibody responses, and the seroprotection rates after IIVs were moderate to high in pregnant women (range = 65%-96%) and young children (range = 50%-100%), varying between the different influenza types/subtypes and seasons. Studies show vaccine efficacy/effectiveness values of 50%-70% in pregnant women and 20%-90% in young children against lab-confirmed influenza, although the efficacy/effectiveness depended on the study design, host factors, vaccine type, manufacturing practices, and the antigenic match/mismatch between the influenza vaccine strains and the circulating strains. Current evidence suggests that the benefits of IIVs far outweigh the potential risks and that IIVs should be recommended for pregnant women and young children.

Keywords: immunogenicity; inactivated influenza vaccine (IIV); pregnant women; safety; vaccine effectiveness (VE); vaccine efficacy; young children.

Figure 1

Flowchart of the included studies. We accessed 3,727 studies (titles and abstracts) following deletion of duplicates (n = 4). The literature search strategy included the following keywords: “influenza,” “maternal influenza vaccination,” “humans,” “pregnant women,” “young children,” “safety,” “adverse event/effect,” “immunogenicity,” “vaccine efficacy,” “vaccine effectiveness,” and “inactivated influenza vaccines” [and the Boolean operators (OR and AND)]. Eligible studies met the following inclusion criteria: 1) published from database inception to May 27, 2021, and 2) evaluated the safety profiles, immunogenicity, and effectiveness of inactivated influenza vaccines (IIVs) in healthy pregnant women and children <5 years old. Studies were excluded based on the title and abstract; non-peer-reviewed papers were not included. Large-scale studies were included only if the results were stratified for the target population. Studies in non-English language were also accessed. Most of the randomized controlled trials in pregnant women included in this review were conducted in low- and middle-income countries, while observation studies were conducted in high-income countries. Out of 93 suitable studies, the majority evaluated seasonal Northern Hemisphere IIVs, even when a study was conducted in the Southern Hemisphere, and 12 studies evaluated H1N1-pdm09 infection and/or vaccination. Of these 93 studies, 36 were on IIV safety, 10 on immunogenicity in pregnant women (two studies assessed both safety and immunogenicity), 16 on immunogenicity in young children (10 studies assessed both safety and immunogenicity), 17 studies for IIV effectiveness in pregnant women (three assessed both immunogenicity and effectiveness and one assessed both safety and effectiveness), and 33 studies for IIV effectiveness in young children (one on both safety and effectiveness and two on both immunogenicity and effectiveness).