Immunogenicity of the Trivalent Inactivated Influenza Vaccine in Young Children Less than 4 Years of Age, with a Focus on Age and Baseline Antibodies

Abstract

fIn this study, we assessed the effects of the prevaccination titer and age on the immunogenicity of a low dose of influenza vaccine in children less than 4 years of age. A total of 259 children received two vaccine doses (0.1 ml for 0-year-olds and 0.2 ml for children 1 year of age or older) 4 weeks apart during the 2005/2006 season. The hemagglutination inhibition antibody titers were measured before vaccination and 4 weeks after the first and second doses. The geometric mean titer, mean fold rise, seroresponse proportion (>4-fold rise in titer), and seroprotection proportion (titer >1:40) were calculated for the prevaccination titer and age categories. A multivariate logistic regression analysis was performed using the seroresponse and seroprotection proportions as dependent variables and the prevaccination titer and age as explanatory variables. As for the seroresponse against the H1 antigen after the first dose, the adjusted odds ratios of the prevaccination titers (versus <1:10) were 2.2 (95% confidence interval, 0.8 to 5.8) at 1:10 to 1:20 and 0.14 (0.04 to 0.49) at >1:40. The corresponding figures for ages were 0.03 (0.01 to 0.07) for the 0-year-olds and 0.17 (0.08 to 0.34) for the 1-year-olds compared with the 2-to 3-year-olds (P trend < 0.001). Similar results were also obtained for the H3 and B strains. Significantly elevated odds ratios for seroprotection were observed with greater prevaccination titers and older ages for all strains. The prevaccination titer and age were independently associated with the antibody response in young children. The immune response was weaker in the younger children and those without preexisting immunity. Influenza is a vaccine-preventable disease. The rate of seasonal influenza infection is highest among children, and children less than 2 years of age are at high risk of influenza-associated hospitalization (1, 2). The Advisory Committee on Immunization Practices routinely recommends that children 6 months to 8 years of age receive two doses of influenza vaccine during their first season of vaccination in order to optimize the immune response (3). This recommendation is based on data showing that vaccine effectiveness and immunogenicity are lower among young children treated with one dose of the vaccine, whereas two doses of vaccine provide substantial protection against influenza-like illness (ILI) (4-6) and induce a protective level of antibodies, even in young children (7-15).The factors affecting low immune responses to the influenza vaccine among children are supposed to include immature immunity function due to age, infrequency of opportunity for exposure to influenza virus through vaccination and/or infection, thus resulting in a lack of induced priming, and a low-volume dose of the vaccine. As the subjects get older, it has been reported that their prevaccination titer (pretiter) increases (16-19), but there has been very little detailed research that considered the predictive factors in the immune response (20,21).In this report, we present the immunogenicity o...

Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh

“…Compared with the VE among adults or in older children, the modest VE we observed may be reflective of lower immunogenicity of non-adjuvanted inactivated influenza vaccines in young children [5] , [23] , [24] , [25] , [26] , [27] . Phase II immunogenicity studies have shown that young children 6–11 months have lower geometric mean antibody titers and lower rates of seroprotection than older children [5] , [23] , [25] , [28] , [29] .…”

Prior vaccinations improve immunogenicity of inactivated influenza vaccine in young children aged 6 months to 3 years

“…We previously reported that younger age was a predictor of lower immunogenicity of IIV independent of baseline antibody titer level, as a result of a study of Japanese children aged 6 months to 3 years in the 2005/2006 season. [ 17 ] Since the dosage of IIV used in the 2005/2006 study was below the current standard, especially for 0-year-olds (0.1 mL/dose vs 0.25 mL/dose), the possibility remains that the lower response at the younger age was due to the low dosage. This interpretation of the result had been consistent with a previous study in Japanese children.…”

Factors That Influence the Immune Response to Vaccination

“…Lower vaccine responses in elderly people Humoral responses aP: GMTs (52,53) HepB: SPRs (55) OPV: SPRs (15) Diphtheria: SPRs (16) OPV: SPRs (15) Tetanus: SPRs (16) wP: SPRs (16) Diphtheria: SPRs (60) HepA: GMTs (61,63,65,142), SCRs (63,76), SPRs (61,62,65,142) HepB: GMTs (61,69,71,73,75,77), SCRs (70,71,75,80,110), SPRs (61, 62, 66-69, 72-75, 77-79, 81) PPV23: GMTs (82-84) TBE: GMTs (88) Tetanus: GMTs (88), SPRs (60,89) TIV: GMTs (87) Cellular responses BCG: Th1, Th2, Treg responses (18) BCG: CD4 T cell response (17) TIV: Th cell and cytotoxic T cell responses (86), lymphoproliferative responses (87) Cytokine responses BCG: IL-6 and IL-17 production (18) TIV: IL-2 (85), IL-10 (87), and IFN-␥ (87) production age than in younger children (93), and GMTs after meningococcal conjugate vaccine (MCV-C) vaccination are higher in children over the age of 10 years than in younger children …”

“…Individuals with higher prevaccination tetanus antibody titers have higher SPRs after booster vaccination (60), while the antibody response to diphtheria is not affected by prevaccination titers (391). Similarly, the antibody response to TIV is positively associated with prevaccination titers (93). Elderly people who have low antibody titers against influenza virus before vaccination might not seroconvert after one dose of TIV (392).…”