Split-Virus Vaccine Better of Two H1N1 Shots

Of the two vaccines used in the U.K. to protect against pandemic H1N1 influenza, the adjuvanted split-virus vaccine offered better protection for children than the non-adjuvanted whole-virus vaccine, but caused more side effects, a phase II study showed.

After two doses, there were higher seroconversion rates with the adjuvanted vaccine both in children younger than 3 (98.2% versus 80.1%, P<0.001) and in older children (99.1% versus 95.9%, P=0.03), Claire Waddington, a clinical research fellow at the Oxford Vaccine Group in England, and colleagues reported online in BMJ.

Although the researchers said both vaccines were well tolerated, there were higher rates of local and systemic reactions with the adjuvanted vaccine.

Waddington and her colleagues concluded, “The favorable immunogenicity of the adjuvanted split-virion vaccine in the youngest children in our study suggests that novel adjuvants could be used to improve the immunogenicity of seasonal influenza vaccines in this population.”

Children have been heavily affected by the H1N1 pandemic and were in the priority group for vaccination in most countries. But there is little safety and efficacy data for the new vaccines.

Waddington and her colleagues compared the two pandemic vaccines purchased by the U.K. Department of Health, GlaxoSmithKline’s AS03B adjuvanted split-virus vaccine derived from egg culture, which contains 1.875 µg of haemagglutinin antigen, and Baxter’s non-adjuvanted whole-virus vaccine derived from cell culture, which contains 7.5 µg of haemagglutinin.

The study was an open-label, randomized, parallel-group, phase II study conducted at five centers in England during the second wave of the pandemic from September 2009 to December 2009.

Children ages 6 months to 12 years were randomized to receive the adjuvanted vaccine (469 patients) or the whole-virus vaccine (464 patients) administered in two doses 21 days apart.

Seroconversion, defined as four-fold increase to a titer of at least 1:40 from before vaccination to three weeks after the second dose, occurred at higher rates with the adjuvanted vaccine according to both the microneutrilization assay and the haemagglutination inhibition assay.

There was a significant interaction between immunogenicity and age (P<0.001), with a greater effect in younger children for the adjuvanted vaccine and a magnified effect in older children with the whole-virus vaccine.

There were more side effects with the adjuvanted vaccine, including more frequent severe local reactions after both the first (7.2% versus 1.1%) and second (8.5% versus 1.1%) doses in children older than 5 and after the second dose in children younger than 5 (5.9% versus 0%) (P<0.05 for all).

Systemic reactions were also more frequent, including irritability and decreased feeding and activity in children younger than 5, and muscle pain and a state of being generally unwell in children older than 5.

Among younger children, fever of at least 100.4°F was more common with the adjuvanted vaccine after the second dose (22.4% versus 8.9%, P<0.001).

Four adverse events of note occurred, according to the researchers. One, a focal seizure believed to be unrelated to vaccination, occurred with the whole-virus vaccine. Three others occurred with the adjuvanted vaccine -- one case of knee osteoarthritis possibly related to the shots and two generalized seizures believed to be unrelated to vaccination.

The researchers acknowledged some limitations of the study, including the lack of a blood test after the first dose because two doses were recommended at the time, and lack of a non-adjuvanted split-virus vaccine as a comparator.

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The study was funded by the National institute of Health Research (NIHR) Health Technology Assessment Program and was supported by the NIHR Oxford Comprehensive Biomedical Research Center program and the Thames Valley, Hampshire and Isle of Wight and Western Comprehensive Local Research Networks and the Southampton Respiratory NIHR Biomedical Research Unit. The study was adopted by the NIHR Medicines for Children Research Network and supported by their South West and London-South East, North, Central, and East Local Research Networks. One of the study authors is a Jenner Institute Investigator.

Waddington reported no conflicts of interest. Several of the study authors reported receiving research grants and honoraria from and participating on advisory boards for vaccine manufacturers.

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Primary source: BMJ
Source reference: Waddington C, et al “Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in U.K. children aged 6 months-12 years: open-label, randomized, parallel-group, multicenter study” BMJ 2010; DOI: 10.1136/bmj.c2649.