BackgroundAlthough seasonal influenza vaccine is effective in the elderly, immune responses to vaccination are lower in the elderly than in younger adults. Strategies to optimise responses to vaccination in the elderly include using an adjuvanted vaccine or using an intradermal vaccination route. The immunogenicity of an intradermal seasonal influenza vaccine was compared with that of an adjuvanted vaccine in the elderly.MethodsElderly volunteers (age ≥ 65 years) were randomised to receive a single dose of trivalent seasonal influenza vaccine: either a split-virion vaccine containing 15 μg haemagglutinin [HA]/strain/0.1-ml dose administered intradermally, or a subunit vaccine (15 μg HA/strain/0.5-ml dose) adjuvanted with MF59C.1 and administered intramuscularly. Blood samples were taken before and 21 ± 3 days post-vaccination. Anti-HA antibody titres were assessed using haemagglutination inhibition (HI) and single radial haemolysis (SRH) methods. We aimed to show that the intradermal vaccine was non-inferior to the adjuvanted vaccine.ResultsA total of 795 participants were enrolled (intradermal vaccine n = 398; adjuvanted vaccine n = 397). Non-inferiority of the intradermal vaccine was demonstrated for the A/H1N1 and B strains, but not for the A/H3N2 strain (upper bound of the 95% CI = 1.53) using the HI method, and for all three strains by the SRH method. A post-hoc analysis of covariance to adjust for baseline antibody titres demonstrated the non-inferiority of the intradermal vaccine by HI and SRH methods for all three strains. Both vaccines were, in general, well tolerated; the incidence of injection-site reactions was higher for the intradermal (70.1%) than the adjuvanted vaccine (33.8%) but these reactions were mild and of short duration.ConclusionsThe immunogenicity and safety of the intradermal seasonal influenza vaccine in the elderly was comparable with that of the adjuvanted vaccine. Intradermal vaccination to target the immune properties of the skin appears to be an appropriate strategy to address the challenge of declining immune responses in the elderly.Trial registrationClinicalTrials.gov: NCT00554333.

NCT00968526.

BackgroundTyphoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults.MethodologyFollowing randomized blinded comparison of single vaccination with either Vi-CRM197 or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM197 (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine.Principal FindingsAll vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM197 induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM197 formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship.ConclusionsVi-CRM197 did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia.Trial RegistrationClinicalTrials.gov NCT01123941 NCT01193907

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This manuscript presents data on the persistence of Hemagglutination Inhibition (HI) immune response against the A/California/7/2009 strain, six and 12 mo after adults received one dose (n = 138) or two doses (n = 102; 21 d apart) of a 3.75 µg Hemagglutinin antigen AS03-adjuvanted H1N1 2009 vaccine (NCT00968526). Two hundred forty subjects (18-60 y: 120;>60 y: 120) were vaccinated. Immunogenicity end points were based on the European licensure criteria for pandemic influenza vaccines. Exploratory analyses assessed the cell-mediated immune response (CMI) up to Month 12 and the influence of previous influenza vaccination on persistence of immune response. At Month 6, the CHMP criteria were met in subjects aged 18-60 y who received one or two vaccine doses and in subjects aged>60 y who received two vaccine doses. At Month 12, the CHMP criteria were met only in subjects aged 18-60 y who received two vaccine doses. Persistence of HI immune response against the vaccine strain was higher in subjects without prior influenza vaccination. Exploratory analyses showed that two doses of the H1N1 2009 vaccine induced persistence of H1N1-specific CD4+ T cells up to Month 6 and memory B cells up to Month 12. In conclusion, HI immune responses persisted up to 12 mo after vaccination with one-dose and two-dose regimens of the AS03-adjuvanted 3.75 µg HA H1N1 2009 pandemic influenza vaccine, although not all three CHMP guidance criteria for both groups were met at Month 6 and Month 12. The CD4+ T cell and B cell responses also persisted up to Month 12.