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. 2015 Sep:44:112-118.
doi: 10.1016/j.cct.2015.08.006. Epub 2015 Aug 12.

Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost

Julie E Ledgerwood  1 , Zonghui Hu  2 , Pamela Costner  3 , Galina Yamshchikov  4 , Mary E Enama  3 , Sarah Plummer  3 , Cynthia S Hendel  3 , Lasonji Holman  3 , Brenda Larkin  3 , Ingelise Gordon  3 , Robert T Bailer  3 , Donald M Poretz  5 , Uzma Sarwar  3 , Alisha Kabadi  3 , Richard Koup  3 , John R Mascola  3 , Barney S Graham  3 ; VRC 307 and VRC 309 Study Teams
Collaborators, Affiliations

Phase I clinical evaluation of seasonal influenza hemagglutinin (HA) DNA vaccine prime followed by trivalent influenza inactivated vaccine (IIV3) boost

Julie E Ledgerwood et al. Contemp Clin Trials. 2015 Sep.

Abstract

Annual influenza vaccination reduces the risks of influenza when the vaccines are well matched to circulating strains, but development of an approach that induces broader and more durable immune responses would be beneficial. We conducted two companion Phase 1 studies, VRC 307 and VRC 309, over sequential seasons (2008-2009 and 2009-2010) in which only the influenza B strain component of the vaccines differed. Objectives were safety and immunogenicity of prime-boost vaccination schedules. A schedule of DNA vaccine encoding for seasonal influenza hemagglutinins (HA) prime followed by seasonal trivalent influenza inactivated vaccine (IIV3) boost (HA DNA-IIV3) was compared to placebo (PBS)-IIV3 or IIV3-IIV3. Cumulatively, 111 adults were randomized to HA DNA-IIV3 (n=66), PBS-IIV3 (n=25) or IIV3-IIV3 (n=20). Safety was assessed by clinical observations, laboratory parameters and 7-day solicited reactogenicity. The seasonal HA DNA prime-IIV3 boost regimen was evaluated as safe and well tolerated. There were no serious adverse events. The local and systemic reactogenicity for HA DNA, IIV and placebo were reported predominantly as none or mild within the first 5days post-vaccination. There was no significant difference in immunogenicity detected between the treatment groups as evaluated by hemagglutination inhibition (HAI) assay. The studies demonstrated the safety and immunogenicity of seasonal HA DNA-IIV3 regimen, but the 3-4week prime-boost interval was suboptimal for improving influenza-specific immune responses. This is consistent with observations in avian H5 DNA vaccine prime-boost studies in which a long interval, but not a short interval, was associated with improved immunogenicity.

Trial registration: NCT00858611 for VRC 307 and NCT00995982 for VRC 309.

Keywords: DNA vaccine; Immune response; Seasonal influenza.

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Figures

Fig. 1
Fig. 1
CONSORT flow diagram. Study enrollment, allocation and follow-up are shown for all screened and enrolled subjects.
Fig. 2
Fig. 2
Severity of solicited reactogenicity by day as reported by subjects using a 7-day diary card.
See this image and copyright information in PMC

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