Influenza Vaccine Immunogenicity in 6- to 23-Month-Old Children: Are Identical Antigens Necessary for Priming?

Abstract

Although the immune response to the identical A/H1N1 vaccine antigen was similar in both groups, priming with different A/H3N2 antigens and B antigens in the spring produced a lower immune response to both antigens than that shown in children who received 2 doses of the same vaccine in the fall. However, approximately 70% of children in the spring group had a protective response to the H3N2 antigen after 2 doses. Initiating influenza immunization in the spring was superior to 1 dose of trivalent inactivated influenza vaccine in the fall. The goal of delivering 2 doses of influenza vaccine a month apart to vaccine-naive children within the narrow flu vaccination season is a challenge not yet met; thus far, only about half of children aged 6 to 23 months of age are receiving influenza vaccine. By using the spring schedule, we were able to administer 2 doses of trivalent inactivated influenza vaccine to a higher proportion of children earlier in the influenza vaccination season. In years when there is an ample supply of trivalent inactivated influenza vaccine, and vaccine remains at the end of the season, priming influenza vaccine-naive infants with a spring dose will lead to the earlier protection of a higher proportion of infants in the fall. This strategy may be particularly advantageous when there is an early start to an influenza season as occurred in the fall of 2003. A priming dose of influenza vaccine in the spring may also offer other advantages. Many vaccine-naive children may miss the second dose of fall trivalent inactivated influenza vaccine because of vaccine shortages or for other reasons, such as the potential implementation of new antigens at a late date. Even with seasonal changes in influenza vaccine antigens, by giving a springtime dose of trivalent inactivated influenza vaccine, such children would be more protected against influenza than would children who were only able to receive 1 dose in the fall. In summary, our data suggest that identical influenza antigens are not necessary for priming vaccine-naive children and that innovative uses of influenza vaccine, such as a springtime dose of vaccine, could assist in earlier and more complete immunization of young children.

Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children

“…Of the 4,372 studies initially identified (Figure), 18 RCTs [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], 14 non-randomised clinical trials [40][41][42][43][44][45][46][47][48][49][50][51][52][53], and six observational studies [54][55][56][57][58][59] were eligible for inclusion. The clinical trial registry search yielded 12 additional relevant studies (five RCTs and seven nonrandomised trials).…”

“…Classification of fever varied across studies, but a majority of studies [22,25,27,[29][30][31]34,35,37,38] provided data on fever ≥ 38 °C. We used these studies for meta-analysis of fever rate and one additional study [39], where we assumed a fever definition of ≥ 38 °C based on two similar studies by the same lead author [31,35].…”

“…Five studies were assessed as being at low risk of bias [26,31,[33][34][35]. Ten studies had medium risk of bias [22,24,25,[27][28][29][30]32,38,39], and three studies had high risk [23,36,37]. Sensitivity analyses limited only to low-risk studies were not feasible; there were too few studies, and two did not use a fever definition of ≥ 38 °C.…”

“…RCTs using Sanofi Pasteur products (Vaxigrip, Fluzone) [22][23][24][25][26]29,[31][32][33]36,38], GSK's Fluarix [27,32,37], and Novartis's Agrippal [28] were examined (Table 3). Overall, fever rates were comparable between these brands of vaccine.…”

“…Using similar proportion meta-analysis of vaccinated study arms, we calculated an FC rate of 1.1 per 1,000 (95% CI: 0.51-1.9) using three large RCTs [26,32,39] (n = 7,439 children up to 59 or 71 months of age) that specifically reported FC as adverse events, and six RCTs (1,207 children aged up to 59 months) [22,25,29,31,34,38] that reported no related SAEs and by assumption, no FC. One of the three studies that reported on FC [32] included one vaccine-related seizure within a subset of 1,496 children aged 6-59 months (0.67 events per 1,000 children).…”