Coadministration of orally inhaled zanamivir with inactivated trivalent influenza vaccine does not adversely affect the production of antihaemagglutinin antibodies in the serum of healthy volunteers

Objective: Zanamivir, a clinically proven potent and specific inhibitor of influenza A and B neuraminidase, has been approved in some countries for th e treatment of influenza and is in late-stage development for the prophylax is of influenza. This study investigated whether the coadministration of za namivir and influenza vaccine affected the development of antibody response s to injected influenza haemagglutinin. Design: This double-blind randomised placebo-controlled study compared the antihaemagglutinin antibody production [haemagglutination inhibition (HAI) titre] after administration of inactivated trivalent influenza vaccine in h ealthy volunteers receiving zanamivir or placebo once daily for 28 days. Study participants: 138 healthy volunteers (52 men and 86 nonpregnant women , mean age 32.7 years) were randomised to the zanamivir (70 participants) o r placebo (68 participants) groups. Interventions: Participants received a single intramuscular dose (deltoid m uscle) of the 1997/1998 trivalent inactivated influenza vaccine (surface an tigen) PhEur (Fluvirin(TM)) on day I, and were then randomised to receive z anamivir 10 mg/day by oral inhalation or placebo for 28 days. Serum samples for determination of HAI titres were obtained before vaccination and on da ys 15 and 29. Compliance, adverse events and laboratory parameters were mon itored. Results: The primary measure of response was the geometric mean increase in HAI titre against the 3 viral antigens contained in the vaccine, calculate d as the ratio of the value 4 weeks after vaccination to the baseline value . The means land 2-sided 95% confidence intervals) for the ratio between th e geometric mean in crease with placebo and the increase with zanamivir wer e as follows: 1.1 (0.7, 1.5) for influenza B, 0.7 (0.4, 1.2) for influenza A H1N1, and 0.6 (0.4, 1.1) for influenza A H3N2 (This corresponds to a test level of alpha = 0.025 for the hypothesis that the increase with placebo w as greater than or equal to 2-fold greater than the increase with zanamivir .) A lack of effect was concluded as values of 2.0 or greater (i.e. a 2-fol d difference) were excluded. Comparisons were also made of the increase in titre at 2 weeks, the proportions of participants with at least a 4-fold in crease in titre and the proportions of participants with a titre of at leas t 1 : 4.0. These comparisons revealed no differences between zanamivir- and placebo-treated groups. The nature and incidence of adverse events observe d with zanamivir were similar to those observed with placebo. Conclusions: Overall, zanamivir was not associated with a reduced response in HAI titre against the 3 vaccine antigens when compared with placebo. In addition, zanamivir was well tolerated. Inhaled zanamivir 10mg once daily h as been demonstrated to prevent symptomatic laboratory-confirmed influenza in a community outbreak. Zanamivir should have the potential to provide pro tection during the 2- to 4-week period before full immunity is induced, fol lowing vaccination at a time when influenza is circulating in the community .