PMID- 18599164
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20161124
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 26
IP  - 33
DP  - 2008 Aug 5
TI  - Phase I and II randomised trials of the safety and immunogenicity of a prototype 
      adjuvanted inactivated split-virus influenza A (H5N1) vaccine in healthy adults.
PG  - 4160-7
LID - 10.1016/j.vaccine.2008.05.077 [doi]
AB  - OBJECTIVE: The primary objective was to evaluate the safety and immunogenicity of 
      a prototype inactivated, split-virus H5N1 (avian influenza A) vaccine. A 
      secondary objective was to assess the cross-reactivity of immune responses to two 
      variant clade 2 H5N1 strains. METHODS: In two randomised, dose comparison, 
      parallel assignment, multicentre trials conducted in Australia, healthy adult 
      volunteers received two doses of 7.5 microg or 15 microg H5 haemagglutinin (HA) 
      vaccine+/-AlPO4 adjuvant (phase I trial; N=400) or two doses of 30 microg or 45 
      microg H5 HA with AlPO4 adjuvant (phase II trial; N=400). Revaccination with a 
      booster dose was offered 6 months after dose 2 (phase I trial only). Main outcome 
      measures were the change in immunogenicity at each follow-up visit from baseline, 
      measured using HA inhibition (HI) and virus microneutralisation (MN) assays, and 
      the frequency and nature of adverse events (AEs). Computer generated tables were 
      used to randomly allocate treatments; participants and investigators were blinded 
      to treatment allocation. FINDINGS: All formulations were well-tolerated; no 
      unexpected serious adverse events were reported. Two doses of 30 microg or 45 
      microg H5 HA adjuvanted formulations elicited the highest immune responses, with 
      considerable MN antibody (>or=1:20) persistence up to 6 months post-vaccination. 
      The 7.5 and 15 microg formulations (+/-adjuvant) were less immunogenic than the 
      higher dose formulations; HI and MN antibody titres decreased to near 
      pre-vaccination levels at 6 months but were restored to post-dose 2 levels after 
      the booster dose. Immune responses in the phase I trial demonstrated modest 
      levels of cross-protective MN antibodies against two currently circulating, 
      distinct clade 2 H5N1 strains. INTERPRETATION: Two doses of prototype 30 microg 
      or 45 microg aluminium-adjuvanted, clade 1 H5N1 vaccines were immunogenic and 
      well-tolerated with considerable 6-month antibody persistence. The prototype H5N1 
      vaccine also elicited modest levels of cross-protective MN antibodies against 
      variant clade 2 H5N1 strains [ClinicalTrials.gov identifiers: NCT00136331, 
      NCT00320346; FUNDING: CSL Limited, Australia].
FAU - Nolan, Terry M
AU  - Nolan TM
AD  - Murdoch Childrens Research Institute, and the Melbourne School of Population 
      Health, University of Melbourne, Carlton, Victoria, Australia. 
      t.nolan@unimelb.edu.au
FAU - Richmond, Peter C
AU  - Richmond PC
FAU - Skeljo, Maryanne V
AU  - Skeljo MV
FAU - Pearce, Georgina
AU  - Pearce G
FAU - Hartel, Gunter
AU  - Hartel G
FAU - Formica, Neil T
AU  - Formica NT
FAU - Hoschler, Katja
AU  - Hoschler K
FAU - Bennet, Jillian
AU  - Bennet J
FAU - Ryan, David
AU  - Ryan D
FAU - Papanaoum, Kelly
AU  - Papanaoum K
FAU - Basser, Russell L
AU  - Basser RL
FAU - Zambon, Maria C
AU  - Zambon MC
LA  - eng
SI  - ClinicalTrials.gov/NCT00136331
SI  - ClinicalTrials.gov/NCT00320346
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20080613
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Alum Compounds)
RN  - 0 (Antibodies, Viral)
RN  - 0 (Hemagglutinin Glycoproteins, Influenza Virus)
RN  - 0 (Influenza Vaccines)
RN  - 0 (Vaccines, Inactivated)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (hemagglutinin, human influenza A virus)
RN  - 34S289N54E (aluminum sulfate)
SB  - IM
MH  - Adjuvants, Immunologic/administration & dosage
MH  - Adolescent
MH  - Adult
MH  - Alum Compounds/administration & dosage/pharmacology
MH  - Antibodies, Viral/blood
MH  - Australia
MH  - Female
MH  - Hemagglutination Inhibition Tests
MH  - Hemagglutinin Glycoproteins, Influenza Virus/administration & dosage/adverse 
      effects/immunology
MH  - Humans
MH  - Immunization, Secondary
MH  - Influenza A Virus, H5N1 Subtype/*immunology
MH  - Influenza Vaccines/administration & dosage/*adverse effects/*immunology
MH  - Influenza, Human/prevention & control
MH  - Male
MH  - Middle Aged
MH  - Neutralization Tests
MH  - Vaccines, Inactivated/administration & dosage/adverse effects/immunology
MH  - Vaccines, Subunit/administration & dosage/adverse effects/immunology
EDAT- 2008/07/05 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/07/05 09:00
PHST- 2008/04/29 00:00 [received]
PHST- 2008/05/15 00:00 [revised]
PHST- 2008/05/25 00:00 [accepted]
PHST- 2008/07/05 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/07/05 09:00 [entrez]
AID - S0264-410X(08)00692-0 [pii]
AID - 10.1016/j.vaccine.2008.05.077 [doi]
PST - ppublish
SO  - Vaccine. 2008 Aug 5;26(33):4160-7. doi: 10.1016/j.vaccine.2008.05.077. Epub 2008 
      Jun 13.