tetano
Editor, Senior Moderator
Clin Vaccine Immunol. 2012 Sep 5. [Epub ahead of print]
H5 DNA Influenza Vaccination is Immunogenic by Intramuscular and Intradermal Routes in Humans.
Ledgerwood JE, Hu Z, Gordon IJ, Yamshchikov G, Enama ME, Plummer S, Bailer R, Pearce MB, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS; the VRC 304 and VRC 305 Study Teams.
Source
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Abstract
Background. Avian influenza causes outbreaks in domestic and wild birds around the world and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized Phase I clinical studies.Methods. VRC 304 was a double-blinded study with 45 subjects randomized to placebo, 1 mg, or 4 mg vaccine (n=15/group) by intramuscular (IM) Biojector? injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (ID) injections of 0.5 mg by needle/syringe or by Biojector?, or 1 mg delivered as two 0.5 mg Biojector? injections in the same deltoid or as 0.5 mg in each deltoid (n=11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by HAI, ELISA and neutralization assays and H5 T cell responses were assessed by ELISPOT and ICS assays.Results. There were no vaccine-related serious adverse events and the vaccine was well tolerated in all groups. At 1 mg, ID compared to IM vaccination induced greater frequency and magnitude of response by ELISA but there were no significant differences in frequency or magnitude of response between ID and IM routes in the HAI or neutralization assays. T cell responses were more frequent in those who received the 1 mg or 4 mg dose IM.Conclusions. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The ID injection route did not offer a significant advantage over the IM route, and no difference was detected by delivery to one site versus splitting the dose between two sites for ID vaccine administration. The 4 mg dose (IM) has been further investigated in prime-boost regimens.
PMID:
22956656
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22956656
H5 DNA Influenza Vaccination is Immunogenic by Intramuscular and Intradermal Routes in Humans.
Ledgerwood JE, Hu Z, Gordon IJ, Yamshchikov G, Enama ME, Plummer S, Bailer R, Pearce MB, Tumpey TM, Koup RA, Mascola JR, Nabel GJ, Graham BS; the VRC 304 and VRC 305 Study Teams.
Source
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Abstract
Background. Avian influenza causes outbreaks in domestic and wild birds around the world and sporadic human infections have been reported. A DNA vaccine encoding hemagglutinin (HA) protein from the A/Indonesia/5/05 (H5N1) strain was initially tested in two randomized Phase I clinical studies.Methods. VRC 304 was a double-blinded study with 45 subjects randomized to placebo, 1 mg, or 4 mg vaccine (n=15/group) by intramuscular (IM) Biojector? injection. VRC 305 was an open-label study to evaluate route, with 44 subjects randomized to intradermal (ID) injections of 0.5 mg by needle/syringe or by Biojector?, or 1 mg delivered as two 0.5 mg Biojector? injections in the same deltoid or as 0.5 mg in each deltoid (n=11/group). Injections were administered at weeks 0, 4, and 8 in both studies. Antibody responses to H5 were assessed by HAI, ELISA and neutralization assays and H5 T cell responses were assessed by ELISPOT and ICS assays.Results. There were no vaccine-related serious adverse events and the vaccine was well tolerated in all groups. At 1 mg, ID compared to IM vaccination induced greater frequency and magnitude of response by ELISA but there were no significant differences in frequency or magnitude of response between ID and IM routes in the HAI or neutralization assays. T cell responses were more frequent in those who received the 1 mg or 4 mg dose IM.Conclusions. These studies demonstrated that the DNA vaccine encoding H5 is safe and immunogenic and served to define the proper dose and route for further studies. The ID injection route did not offer a significant advantage over the IM route, and no difference was detected by delivery to one site versus splitting the dose between two sites for ID vaccine administration. The 4 mg dose (IM) has been further investigated in prime-boost regimens.
PMID:
22956656
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22956656