Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect

Julie E. Ledgerwood; Kathryn Zephir; Zonghui Hu; Chih Jen Wei; Leejah Chang; Mary E. Enama; Cynthia S. Hendel; Sandra Sitar; Robert T. Bailer; Richard A. Koup; John R. Mascola; Gary J. Nabel; Barney S. Graham

doi:10.1093/infdis/jit180

Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect

Julie E. Ledgerwood, Kathryn Zephir, Zonghui Hu, Chih Jen Wei, Leejah Chang, Mary E. Enama, Cynthia S. Hendel, Sandra Sitar, Robert T. Bailer, Richard A. Koup, John R. Mascola, Gary J. Nabel, Barney S. Graham

Research output: Contribution to journal › Article › peer-review

85 Scopus citations

Abstract

Background. H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.Methods. We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).Results. H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).Conclusion. H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks.Clinical Trials Registration. NCT01086657.

Original language	English (US)
Pages (from-to)	418-422
Number of pages	5
Journal	Journal of Infectious Diseases
Volume	208
Issue number	3
DOIs	https://doi.org/10.1093/infdis/jit180
State	Published - Aug 1 2013
Externally published	Yes

Keywords

Avian influenza
boost interval
DNA vaccine
H5N1
hemagglutination inhibition

ASJC Scopus subject areas

Infectious Diseases
Immunology and Allergy

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10.1093/infdis/jit180

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Ledgerwood, J. E., Zephir, K., Hu, Z., Wei, C. J., Chang, L., Enama, M. E., Hendel, C. S., Sitar, S., Bailer, R. T., Koup, R. A., Mascola, J. R., Nabel, G. J., & Graham, B. S. (2013). Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect. Journal of Infectious Diseases, 208(3), 418-422. https://doi.org/10.1093/infdis/jit180

Ledgerwood, JE, Zephir, K, Hu, Z, Wei, CJ, Chang, L, Enama, ME, Hendel, CS, Sitar, S, Bailer, RT, Koup, RA, Mascola, JR, Nabel, GJ & Graham, BS 2013, 'Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect', Journal of Infectious Diseases, vol. 208, no. 3, pp. 418-422. https://doi.org/10.1093/infdis/jit180

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abstract = "Background. H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.Methods. We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).Results. H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).Conclusion. H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks.Clinical Trials Registration. NCT01086657.",

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author = "Ledgerwood, {Julie E.} and Kathryn Zephir and Zonghui Hu and Wei, {Chih Jen} and Leejah Chang and Enama, {Mary E.} and Hendel, {Cynthia S.} and Sandra Sitar and Bailer, {Robert T.} and Koup, {Richard A.} and Mascola, {John R.} and Nabel, {Gary J.} and Graham, {Barney S.}",

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AU - Zephir, Kathryn

AU - Hu, Zonghui

AU - Wei, Chih Jen

AU - Chang, Leejah

AU - Enama, Mary E.

AU - Hendel, Cynthia S.

AU - Sitar, Sandra

AU - Bailer, Robert T.

AU - Koup, Richard A.

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AU - Nabel, Gary J.

AU - Graham, Barney S.

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AB - Background. H5 DNA priming was previously shown to improve the antibody response to influenza A(H5N1) monovalent inactivated vaccine (MIV) among individuals for whom there was a 24-week interval between prime and boost receipt. This study defines the shortest prime-boost interval associated with an improved response to MIV.Methods. We administered H5 DNA followed by MIV at intervals of 4, 8, 12, 16, or 24 weeks and compared responses to that of 2 doses of MIV (prime-boost interval, 24 weeks).Results. H5 DNA priming with an MIV boost ≥12 weeks later showed an improved response, with a positive hemagglutination inhibition (HAI) titer in 91% of recipients (geometric mean titer [GMT], 141-206), compared with 55%-70% of recipients with an H5 DNA and MIV prime-boost interval of ≤8 weeks (GMT, 51-70) and 44% with an MIV-MIV prime-boost interval of 24 weeks (GMT, 27).Conclusion. H5 DNA priming enhances antibody responses after an MIV boost when the prime-boost interval is 12-24 weeks.Clinical Trials Registration. NCT01086657.

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KW - hemagglutination inhibition

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Prime-boost interval matters: A randomized phase 1 study to identify the minimum interval necessary to observe the h5 dna influenza vaccine priming effect

Abstract

Keywords

ASJC Scopus subject areas

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