Investigators: Chris Blyth, Tobi Kollmann, Peter Richmond, Ushma Wadia, Mario Fidanza
Summary
Influenza is the number one notifiable vaccine preventable diseases in Australia with the greatest burden impacting infants under 6 months of age, who do not receive the influenza vaccine under the national vaccine schedule. This phase 2 clinical trial will assess the safety and immune response in infants less than 6 months of age who receive the current influenza vaccine (QIV). The impact of the Mothers influenza vaccination status or infection with influenza while pregnant will also be assessed. This study will inform a larger clinical trial and help provide evidence for influenza vaccination policy in infants under 6 months of age.
Project description
Influenza is the most common vaccine-preventable disease and a major cause of hospitalisation, morbidity and mortality globally. Young children, particularly those younger than 6 months of age, are at heightened risk of severe influenza. Babies can be at least partially protected during this period of increased vulnerability by the presence of maternal antibodies. However, while the positive effect of this protective mechanism is evident in the reduction in infant hospitalisations and death following maternal vaccination against influenza, the presence of maternal antibodies is also believed to have a significant impact on primary humoral immune responses in the newborn.
The fact that maternal antibodies have been seen to decrease the magnitude of infant vaccine responses (blunting) has led many experts to conclude that this impact was solely negative. However, emerging data suggest that:
- blunting by maternal antibodies does not affect the antimicrobial effector functions induced by the infant
- maternal antibodies do not inhibit the generation of memory B cells which are critical to subsequent viral protection
- immunisation under the cover of maternal antibodies may actually increase the breadth, longevity and protective capacity of infant vaccine responses.
To assess both the safety of the seasonal influenza vaccine administered earlier in life as well as the impact of maternal antibodies on in influenza vaccine responses; we are running a clinical trial to test the safety of administering the influenza vaccine 3-4 months earlier than the current recommendation. This trial will also tell us whether early influenza vaccination offers the same level of protection as when it is given after age 6 months and provide insight into how the presence of maternal anti-influenza antibodies quantitatively and qualitatively influences infant influenza vaccine responses and subsequent immune profiles.
This is a pilot study that will tell us whether a larger, more informative study will be worthwhile. We aim to have 150 babies allocated to one of three influenza vaccination schedules:
- Arm 1: Early vaccination & booster (vaccine at 2-3 months of age; a booster one month later);
- Arm 2: Early vaccination & delayed booster (vaccine at 2-3 months; a booster at 7-8 months of age);
- Arm 3: Standard vaccination (vaccine at 6-7 months; a booster one month later).
This study will give us valuable information about how influenza vaccines work, to help researchers to develop new vaccines that offer better protection for everyone. We will look at how the timing of vaccination changes protective responses both after the first vaccination and during the following influenza season, as well as how a mother’s influenza infection and/or vaccination history might influence how well influenza vaccines work in their babies.
This clinical trial has been registered with the Australia New Zealand Clinical Trials Registry (ACTRN12620000644965)