Trial reportThe Lancet. Infectious diseases2011
DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials.
Trial report in The Lancet. Infectious diseases, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Cited by 131 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Randomized Phase I Study in Healthy Adults of 4 Prime-Boost Schedules With Monovalent Influenza Subunit Virion (H5N1) Vaccine (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant DNA Plasmid (H5) Vaccine (VRC, NIAID)
VRC 310: An Open-Label, Randomized Ph I: Healthy Adults of Prime-Boost Intervals w/Monovalent Influenza Virion (H5N1) Vaccine, A/Indonesia/05/2005 (Sanofi Pasteur, Inc), Administered Alone or Following Recombinant H5 DNA Vaccine
Double-Blind, Randomized Phase 1b Study of 2011/12 Influenza Investigational DNA Vaccine, VRC-FLUDNA061-00-VP, Followed by 2012/13 Trivalent Inactivated Vaccine (TIV) Compared to 2012/13 TIV Alone in Healthy Adults
Open-Label, Dose-Escalation, Phase I Study of the Prime-Boost Investigational 2012/13 Seasonal Influenza DNA Vaccine, VRC-FLUDNA063-00-VP, Followed by the 2012/2013 Seasonal TIV Compared to TIV Prime-Boost in Children/Adolescents Ages 6-17
Open-Label, Randomized Phase 1b Study of the Safety & Immunogenicity of Investigational Seasonal Influenza DNA Vaccine Followed by TIV Administered Intradermally (ID) or Intramuscularly (IM) in Healthy Adults 18-70 Years
VRC 315: A Phase I Open-Label, Randomized Study of H7 Influenza Prime-Boost Regimens in Healthy Adults: Recombinant H7 DNA Plasmid Vaccine, VRC-FLUDNA071-00-VP, Administered Alone or With Monovalent Influenza Subunit Virion H7N9 Vaccine (MIV) as Prime With MIV Boost Compared to MIV Prime With MIV Boost
Who cites it
131 citing papers in PubMed, 189 citations in OpenAlex.
- Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.Vaccine · 2025Trial
- Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial.Nature medicine · 2022Trial
- Trial
- Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials.Lancet (London, England) · 2018Trial
- Trial
- Assessment of immune responses to H5N1 inactivated influenza vaccine among individuals previously primed with H5N2 live attenuated influenza vaccine.Human vaccines & immunotherapeutics · 2015Trial
- DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial.PloS one · 2015Trial
- Induction of broadly cross-reactive antibody responses to the influenza HA stem region following H5N1 vaccination in humans.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response.The Journal of infectious diseases · 2014Trial
- Trial
- Prime-boost interval matters: a randomized phase 1 study to identify the minimum interval necessary to observe the H5 DNA influenza vaccine priming effect.The Journal of infectious diseases · 2013Trial
- Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study.The Lancet. Infectious diseases · 2013Trial
- Trial
- Influenza virus h5 DNA vaccination is immunogenic by intramuscular and intradermal routes in humans.Clinical and vaccine immunology : CVI · 2012Trial
- Randomization to standard and concise informed consent forms: development of evidence-based consent practices.Contemporary clinical trials · 2012Trial
- Article
- A broadly neutralizing antibody confers cross-genus protection against alphaherpesviruses by inhibiting gB-mediated membrane fusion.Nature communications · 2025Article
- Screening for next generation vaccines in human immune organoids.ImmunoHorizons · 2025Review
- Cross-neutralizing and potent human monoclonal antibodies against historical and emerging H5Nx influenza viruses.Nature microbiology · 2025Article
- Immune history shapes human antibody responses to H5N1 influenza viruses.Nature medicine · 2025Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundBecause the general population is largely naive to H5N1 influenza, antibodies generated to H5 allow analysis of novel influenza vaccines independent of background immunity from previous infection. We assessed the safety and immunogenicity of DNA encoding H5 as a priming vaccine to improve antibody responses to inactivated influenza vaccination.
methodsIn VRC 306 and VRC 310, two sequentially enrolled phase 1, open-label, randomised clinical trials, healthy adults (age 18-60 years) were randomly assigned to receive intramuscular H5 DNA (4 mg) at day 0 or twice, at day 0 and week 4, followed by H5N1 monovalent inactivated vaccine (MIV; 90 μg) at 4 or 24 weeks, and compared with a two-dose regimen of H5N1 MIV with either a 4 or 24 week interval. Antibody responses were assessed by haemagglutination inhibition (HAI), ELISA, neutralisation (ID(80)), and immunoassays for stem-directed antibodies. T cell responses were assessed by intracellular cytokine staining. After enrolment, investigators and individuals were not masked to group assignment. VRC 306 and VRC 310 are registered with ClinicalTrials.gov, numbers NCT00776711 and NCT01086657, respectively.
findingsIn VRC 306, 60 individuals were randomly assigned to the four groups (15 in each) and 59 received the vaccinations. In VRC 310, of the 21 individuals enrolled, 20 received the vaccinations (nine received a two-dose regimen of H5N1 MIV and 11 received H5 DNA at day 0 followed by H5N1 MIV at week 24). H5 DNA priming was safe and enhanced H5-specific antibody titres following an H5N1 MIV boost, especially when the interval between DNA prime and MIV boost was extended to 24 weeks. In the two studies, DNA priming with a 24-week MIV boost interval induced protective HAI titres in 21 (81%) of 26 of individuals, with an increase in geometric mean titre (GMT) of more than four times that of individuals given the MIV-MIV regimen at 4 or 24 weeks (GMT 103-206 vs GMT 27-33). Additionally, neutralising antibodies directed to the conserved stem region of H5 were induced by this prime-boost regimen in several individuals. No vaccine-related serious adverse events were recorded.
interpretationDNA priming 24 weeks in advance of influenza vaccine boosting increased the magnitude of protective antibody responses (HAI) and in some cases induced haemagglutinin-stem-specific neutralising antibodies. A DNA-MIV vaccine regimen could enhance the efficacy of H5 or other influenza vaccines and shows that anti-stem antibodies can be elicited by vaccination in man.
fundingNational Institutes of Health.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.