BACKGROUND: Vaccines against pandemic A/H1N1 influenza are required to protect the entire population. This dose range study aimed to identify priming antigen and adjuvant doses resulting in optimal levels of antibody-mediated protection after primary and one-year booster immunizations. METHODS: This randomised trial enrolled 410 healthy adult (18-60 years) and 251 healthy elderly (>60 years) participants. Subjects received vaccine containing either 3.75 μg or 7.5 μg antigen, adjuvanted with half the standard dose, or a standard dose of MF59(®) (Novartis Vaccines) adjuvant, respectively. An additional adult cohort received non-adjuvanted vaccine containing 15 μg antigen. Two doses of investigational vaccine were administered three weeks apart, followed by a single booster dose of adjuvanted seasonal influenza vaccine one year after priming. Immunogenicity was assessed by haemagglutination inhibition and microneutralization assays pre- and post-immunization, the safety profile of each vaccine was also evaluated. RESULTS: All of the vaccine formulations investigated were highly immunogenic and well tolerated in both adult and elderly subjects. The 7.5 μg formulation induced the highest antibody titres after primary and booster immunizations, and resulted in better long-term antibody persistence, in both age groups. Assessment according to European licensure criteria for influenza vaccines concluded that single adjuvanted priming doses containing 3.75 μg and 7.5 μg antigen were optimal for the adult and elderly populations, respectively. CONCLUSIONS: These data demonstrate that one priming dose of MF59-adjuvanted A/H1N1 vaccine provided healthy adult (3.75 μg or 7.5 μg formulations) and healthy elderly (7.5 μg formulation) individuals with adequate levels of seroprotection. Booster administration after two priming doses of either vaccine formulation resulted in the rapid development of seroprotective antibody titres. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00971906).
RCT Entities:
BACKGROUND: Vaccines against pandemic A/H1N1 influenza are required to protect the entire population. This dose range study aimed to identify priming antigen and adjuvant doses resulting in optimal levels of antibody-mediated protection after primary and one-year booster immunizations. METHODS: This randomised trial enrolled 410 healthy adult (18-60 years) and 251 healthy elderly (>60 years) participants. Subjects received vaccine containing either 3.75 μg or 7.5 μg antigen, adjuvanted with half the standard dose, or a standard dose of MF59(®) (Novartis Vaccines) adjuvant, respectively. An additional adult cohort received non-adjuvanted vaccine containing 15 μg antigen. Two doses of investigational vaccine were administered three weeks apart, followed by a single booster dose of adjuvanted seasonal influenza vaccine one year after priming. Immunogenicity was assessed by haemagglutination inhibition and microneutralization assays pre- and post-immunization, the safety profile of each vaccine was also evaluated. RESULTS: All of the vaccine formulations investigated were highly immunogenic and well tolerated in both adult and elderly subjects. The 7.5 μg formulation induced the highest antibody titres after primary and booster immunizations, and resulted in better long-term antibody persistence, in both age groups. Assessment according to European licensure criteria for influenza vaccines concluded that single adjuvanted priming doses containing 3.75 μg and 7.5 μg antigen were optimal for the adult and elderly populations, respectively. CONCLUSIONS: These data demonstrate that one priming dose of MF59-adjuvanted A/H1N1 vaccine provided healthy adult (3.75 μg or 7.5 μg formulations) and healthy elderly (7.5 μg formulation) individuals with adequate levels of seroprotection. Booster administration after two priming doses of either vaccine formulation resulted in the rapid development of seroprotective antibody titres. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00971906).
Authors: H Bisgaard; N H Vissing; C G Carson; A L Bischoff; N V Følsgaard; E Kreiner-Møller; B L K Chawes; J Stokholm; L Pedersen; E Bjarnadóttir; A H Thysen; E Nilsson; L J Mortensen; S F Olsen; S Schjørring; K A Krogfelt; L Lauritzen; S Brix; K Bønnelykke Journal: Clin Exp Allergy Date: 2013-12 Impact factor: 5.018
Authors: Anne Louise Bischoff; Nilofar Vahman Følsgaard; Charlotte Giwercman Carson; Jakob Stokholm; Louise Pedersen; Maria Holmberg; Amalie Bisgaard; Sune Birch; Theodore F Tsai; Hans Bisgaard Journal: PLoS One Date: 2013-04-18 Impact factor: 3.240
Authors: Nicos Karasavvas; Chitraporn Karnasuta; Hathairat Savadsuk; Sirinan Madnote; Dutsadee Inthawong; Somsak Chantakulkij; Surawach Rittiroongrad; Sorachai Nitayaphan; Punnee Pitisuttithum; Prasert Thongcharoen; Vinai Siriyanon; Charla A Andrews; Susan W Barnett; James Tartaglia; Faruk Sinangil; Donald P Francis; Merlin L Robb; Nelson L Michael; Viseth Ngauy; Mark S de Souza; Robert M Paris; Jean-Louis Excler; Jerome H Kim; Robert J O'Connell Journal: AIDS Res Hum Retroviruses Date: 2015-09-09 Impact factor: 2.205