Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion and non-adjuvanted whole virion H1N1 (2009) pandemic influenza vaccines.

In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38 °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.

The immunogenicity of a novel A (H1N1) vaccine in HIV-infected children.

BACKGROUND: In October 2009, the United Kingdom Department of Health recommended vaccination of high-risk groups, including children with HIV, with a novel, oil-in-water AS03(B) adjuvanted Influenza A (H1N1) vaccine (Pandemrix). There were no published data available regarding the immunogenicity of this vaccine in such children. OBJECTIVES: This study evaluated the immunogenicity of the adjuvanted Influenza A (H1N1) vaccine in HIV-infected children immunised according to national recommendations and assessed the impact of vaccination on individual CD4 counts and HIV viral loads. METHODS: HIV-infected children attending outpatient appointments between 01 November and 31 December 2009 were offered two doses of H1N1 vaccine three weeks apart and a blood test before and 3 weeks after the second dose of vaccine. Serum antibody responses were determined by a haemagglutination inhibition (HAI) assay using standard methods. RESULTS: Of the 39 children recruited for vaccination, 31 (median age 11.2, range 3.0-17.9 years) received both doses of vaccine and provided pre- and post-vaccination blood samples. Eight children (26%) had baseline HAI titres ≥ 1:32. After vaccination, 29 children (94%, 95% CI, 78.6-99.2%) had HAI titres ≥ 1:32 (seroprotection), of whom 27 (87.1%, 95% CI, 70.1-96.4%) had also had a four-fold rise in titres (seroconversion). In the univariate analysis, post-vaccination geometric mean titres (GMTs) were higher among the 21 children receiving highly active anti-retroviral therapy compared with the 10 treatment-naïve children (GMT 406 [95% CI 218-757] vs. 128 [49-336]; P=0.035), but this was no longer statistically significant when adjusted for prevaccine GMTs. There was no significant impact of vaccination on CD4+ T cell count or HIV viral load. CONCLUSION: The AS03(B)-adjuvanted pandemic Influenza A (H1N1) vaccine is highly immunogenic and appears to be safe in HIV-infected children.

Immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer in the United Kingdom.

BACKGROUND: Children with cancer have an increased susceptibility to influenza infection. The objective of this study was to assess the immunogenicity of pandemic (H1N1) 2009 vaccine in children with cancer. METHODS: Children were recruited from the Royal Marsden Hospital, England, during November 2009. The vaccination schedule consisted of 2 doses of an AS03(B)-adjuvanted vaccine given at days 0 and 21. Serological analysis was performed on blood samples obtained at day 0 and day 42. The primary immunological end point was the seroconversion rate, which was defined as the proportion of subjects with an individual 4-fold increase in hemagglutination inhibition titer and a postvaccination hemagglutination inhibition titer ≥1:32. RESULTS: Fifty-four children with a median age of 6.3 years (range, 1.4-16.6 years) were vaccinated and had samples taken for serological analysis. Twenty-four (44.4%) of 54 children demonstrated seroconversion. Seroconversion rates were 33.3% (9 of 27) among children with acute lymphoblastic leukemia, 36.4% (4 of 11) among those with lymphoma or other leukemias, 66.7% (6 of 9) among those with brain tumors, and 71.4% (5 of 7) among those with other solid tumors. Seroconversion occurred in 4 (28.6%) of 14 children receiving acute lymphoblastic leukemia maintenance therapy. Univariate analysis showed significantly higher responses among children with solid tumors, compared with those with hematological malignancies (11 [68.8%] of 16 vs 13 [34.2%] of 38; P = .03), and among those not receiving treatment, compared with those receiving treatment (7 [87.5%] of 8 vs 17 [37.0%] of 46; P = .02). Multivariable analysis showed that age, cancer type, and lymphopenia did not influence seroconversion rates. CONCLUSION: These data suggest that this AS03(B)-adjuvanted pandemic (H1N1) 2009 vaccine can induce limited but useful protective immune responses in children with cancer.