The H1N1 Influenza Centre section, a resource of the New England Journal of Medicine website, features new research on the influenza A (H1N1) 2009 monovalent vaccine. This consists of two studies providing the eagerly anticipated preliminary data on the immunogenicity of the vaccine, and a third study examined antibody response to the pandemic virus resulting from previous influenza infection or vaccination in different age groups.
The first report describes a randomised, observer-blind, parallel-group trial evaluating two doses of an inactivated, split-virus 2009 H1N1 vaccine in healthy adults aged18 to 64 years at a single site in Australia. It involved 240 subjects divided into two age groups (< 50 years and ≥ 50 years) randomised to receive either 15mcg or 30mcg of haemagglutinin antigen (HA) by intramuscular injection. The immunogenicity and safety of the vaccine was evaluated 21 days after the first of two scheduled doses; the co-primary immunogenicity end points were the proportion of subjects with antibody titres of 1:40 or more on haemagglutination-inhibition assay, the proportion of subjects with either seroconversion or a significant increase in antibody titre, and the factor increase in the geometric mean titre. By day 21 after vaccination, antibody titres of 1:40 or more were observed in 116 of 120 subjects (96.7%) who received the 15mcg dose and in 112 of 120 subjects (93.3%) who received the 30mcg dose. There were no deaths, serious adverse events, or adverse events of special interest reported. Local discomfort (e.g. injection-site tenderness or pain) was reported by 46.3% of subjects, and systemic symptoms (e.g. headache) by 45% of subjects. The researchers suggest from these preliminary findings that “a single 15mcg dose of 2009 H1N1 vaccine was immunogenic in adults, with mild-to-moderate vaccine-associated reactions.”
The second report describes a single-centre British study assessing a monovalent influenza A/California/2009 (H1N1) surface-antigen vaccine, in both MF59-adjuvanted and non-adjuvanted forms. The study involved 175 adults aged 18 to 50 years of age, randomised to receive one of the following:
• Two IM injections of vaccine containing 7.5mcg of haemagglutinin on day 0 in each arm or one injection on day 0 and the other on day 7, 14, or 21
• Two 3.75mcg doses of MF59-adjuvanted vaccine
• 7.5 or 15mcg of non-adjuvanted vaccine, administered 21 days apart
Antibody responses were measured on days 0, 14, 21, and 42 after injection of the first dose. An interim analysis of the responses to the 7.5mcg dose of MF59-adjuvanted vaccine by days 14 and 21 are presented in this report (data from four of the seven groups studied, for a total of 100 subjects).
The most frequent local and systemic reactions were pain at the injection site and muscle aches, in 70% and 42% of subjects, respectively. Two subjects reported fever, with a temperature of 38°C or higher, after the first dose. Antibody titres were generally higher at day 14 among subjects who had received two 7.5mcg doses of the MF59-adjuvanted vaccine than among those who had received only one by this time point (p = 0.04 haemagglutination-inhibition assay and p < 0.001 microneutralisation assay). By 21 days after vaccination with the first dose of 7.5 mcg of MF59-adjuvanted vaccine, the rates of seroconversion, as measured with the use of a haemagglutination-inhibition assay and a microneutralisation assay, were 76% and 92% of subjects, respectively, who had received only one dose to date (with second dose scheduled for day 21) and 88% to 92% and 92% to 96% of subjects, respectively, who had already received both doses (p = 0.11 and p = 0.64, respectively). The researchers suggest that according to this preliminary analyses, “the monovalent influenza A (H1N1) 2009 MF59-adjuvanted vaccine generates antibody responses likely to be associated with protection within 14 days after a single dose is administered.”
In the third report, researchers from the CDC in Atlanta, assessed the level of pre-existing immunity in humans and evaluated seasonal vaccine strategies. They measured cross-reactive antibodies to pandemic H1N1 virus (2009 H1N1) in stored serum samples from persons who either donated blood or were vaccinated with recent seasonal or 1976 swine influenza vaccines. The following findings were noted:
• 4 of 107 subjects (4%) who were born after 1980 had pre-existing cross-reactive antibody titres of ≥ 40 against 2009 H1N1, vs. 39 of 115 persons (34%) born before 1950 who had titres of ≥ 80
• Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of cross-reactive antibody to 2009 H1N1 by a factor of ≥4 in none of 55 children between the ages of 6 months and 9 years, in 12% to 22% of 231 adults between the ages of 18 and 64 years, and in ≤ 5% of 113 adults 60 years of age or older.
• Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses.
• Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults.
The researchers concluded that “vaccination with recent seasonal non-adjuvanted or adjuvanted influenza vaccines induced little or no cross-reactive antibody response to 2009 H1N1 in any age group. Persons under the age of 30 years had little evidence of cross-reactive antibodies to the pandemic virus. However, a proportion of older adults had pre-existing cross-reactive antibodies.”
An accompanying editorial notes that in the current global situation, in which demand for influenza vaccine greatly exceeds supply, dose-sparing strategies are needed- use of fewer or partial doses and the use of adjuvants, can all contribute to increased global vaccine supply. These studies therefore provide evidence that such strategies may be successful for the current pandemic. The author also discusses immunogenicity in different patient groups, safety and suggested vaccine policy in the US.
A Behind the Headlines assessment from NHS Choices discusses the main study and associated press reports - please see the link below for details.