Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial

Uzma N. Sarwar; Laura Novik; Mary E. Enama; Sarah A. Plummer; Richard A. Koup; Martha C. Nason; Robert T. Bailer; Adrian B. McDermott; Mario Roederer; John R. Mascola; Julie E. Ledgerwood; Barney S. Graham; Elizabeth Adams; Nina Berkowitz; Joseph Casazza; Pamela Costner; Ingelise Gordon; Cynthia Starr Hendel; Lasonji Holman; Brenda Larkin; Susan Leitman; Floreliz Mendoza; Jamie Saunders; Sandra Sitar; Brandon Wilson; Kathryn Zephir; Michelle Conan-Cibotti; Hope DeCederfelt; Judith Starling; Phyllis Renehan; Meghan Kunchai; Ly Diep; Olga Vasilenko; Galina Yamshchikov

doi:10.1371/journal.pone.0106240

Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial

Uzma N. Sarwar, Laura Novik, Mary E. Enama, Sarah A. Plummer, Richard A. Koup, Martha C. Nason, Robert T. Bailer, Adrian B. McDermott, Mario Roederer, John R. Mascola, Julie E. Ledgerwood, Barney S. Graham, Elizabeth Adams, Nina Berkowitz, Joseph Casazza, Pamela Costner, Ingelise Gordon, Cynthia Starr Hendel, Lasonji Holman, Brenda LarkinSusan Leitman, Floreliz Mendoza, Jamie Saunders, Sandra Sitar, Brandon Wilson, Kathryn Zephir, Michelle Conan-Cibotti, Hope DeCederfelt, Judith Starling, Phyllis Renehan, Meghan Kunchai, Ly Diep, Olga Vasilenko, Galina Yamshchikov

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

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Abstract

Results: Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boost

Conclusions: Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.

Background: Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.

Methods: Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 10₁₀ PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.

Original language	English (US)
Article number	e106240
Journal	PloS one
Volume	9
Issue number	9
DOIs	https://doi.org/10.1371/journal.pone.0106240
State	Published - Sep 29 2014
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Sarwar, U. N., Novik, L., Enama, M. E., Plummer, S. A., Koup, R. A., Nason, M. C., Bailer, R. T., McDermott, A. B., Roederer, M., Mascola, J. R., Ledgerwood, J. E., Graham, B. S., Adams, E., Berkowitz, N., Casazza, J., Costner, P., Gordon, I., Hendel, C. S., Holman, L., ... Yamshchikov, G. (2014). Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial. PloS one, 9(9), Article e106240. https://doi.org/10.1371/journal.pone.0106240

Sarwar, UN, Novik, L, Enama, ME, Plummer, SA, Koup, RA, Nason, MC, Bailer, RT, McDermott, AB, Roederer, M, Mascola, JR, Ledgerwood, JE, Graham, BS, Adams, E, Berkowitz, N, Casazza, J, Costner, P, Gordon, I, Hendel, CS, Holman, L, Larkin, B, Leitman, S, Mendoza, F, Saunders, J, Sitar, S, Wilson, B, Zephir, K, Conan-Cibotti, M, DeCederfelt, H, Starling, J, Renehan, P, Kunchai, M, Diep, L, Vasilenko, O & Yamshchikov, G 2014, 'Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial', PloS one, vol. 9, no. 9, e106240. https://doi.org/10.1371/journal.pone.0106240

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title = "Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial",

abstract = "Results: Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boostConclusions: Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Background: Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Methods: Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.",

author = "Sarwar, {Uzma N.} and Laura Novik and Enama, {Mary E.} and Plummer, {Sarah A.} and Koup, {Richard A.} and Nason, {Martha C.} and Bailer, {Robert T.} and McDermott, {Adrian B.} and Mario Roederer and Mascola, {John R.} and Ledgerwood, {Julie E.} and Graham, {Barney S.} and Elizabeth Adams and Nina Berkowitz and Joseph Casazza and Pamela Costner and Ingelise Gordon and Hendel, {Cynthia Starr} and Lasonji Holman and Brenda Larkin and Susan Leitman and Floreliz Mendoza and Jamie Saunders and Sandra Sitar and Brandon Wilson and Kathryn Zephir and Michelle Conan-Cibotti and Hope DeCederfelt and Judith Starling and Phyllis Renehan and Meghan Kunchai and Ly Diep and Olga Vasilenko and Galina Yamshchikov",

note = "Funding Information: We thank the study volunteers and the community advisory board that support the importance of clinical trials evaluating candidate HIV vaccines. We also thank the NIH Clinical Center staff, NIAID IRB, Bioject Inc, EMMES Corporation and other supporting staff (Abe Mittleman, Judy Stein, Carmencita Artis, Richard Jones, Iris Pittman, Diane Johnson, Monique Young, LaChonne Stanford, Sheryl Young) who made this work possible. This study was supported by NIH Intramural Research Program. ",

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doi = "10.1371/journal.pone.0106240",

language = "English (US)",

volume = "9",

journal = "PloS one",

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T1 - Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial

AU - Sarwar, Uzma N.

AU - Novik, Laura

AU - Enama, Mary E.

AU - Plummer, Sarah A.

AU - Koup, Richard A.

AU - Nason, Martha C.

AU - Bailer, Robert T.

AU - McDermott, Adrian B.

AU - Roederer, Mario

AU - Mascola, John R.

AU - Ledgerwood, Julie E.

AU - Graham, Barney S.

AU - Adams, Elizabeth

AU - Berkowitz, Nina

AU - Casazza, Joseph

AU - Costner, Pamela

AU - Gordon, Ingelise

AU - Hendel, Cynthia Starr

AU - Holman, Lasonji

AU - Larkin, Brenda

AU - Leitman, Susan

AU - Mendoza, Floreliz

AU - Saunders, Jamie

AU - Sitar, Sandra

AU - Wilson, Brandon

AU - Zephir, Kathryn

AU - Conan-Cibotti, Michelle

AU - DeCederfelt, Hope

AU - Starling, Judith

AU - Renehan, Phyllis

AU - Kunchai, Meghan

AU - Diep, Ly

AU - Vasilenko, Olga

AU - Yamshchikov, Galina

N1 - Funding Information: We thank the study volunteers and the community advisory board that support the importance of clinical trials evaluating candidate HIV vaccines. We also thank the NIH Clinical Center staff, NIAID IRB, Bioject Inc, EMMES Corporation and other supporting staff (Abe Mittleman, Judy Stein, Carmencita Artis, Richard Jones, Iris Pittman, Diane Johnson, Monique Young, LaChonne Stanford, Sheryl Young) who made this work possible. This study was supported by NIH Intramural Research Program.

PY - 2014/9/29

Y1 - 2014/9/29

N2 - Results: Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boostConclusions: Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Background: Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Methods: Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.

AB - Results: Overall, injections by either method were well tolerated. There were no serious adverse events. Frequency of any local reactogenicity was 16/16 (100%) for Biojector compared to 11/15 (73%) for needle injections. There was no difference in HIV Env-specific antibody response between Biojector and needle delivery. Env-specific antibody responses were more than 10-fold higher in subjects receiving a booster dose of rAd5 vaccine than after a single dose delivered by either method regardless of interval between prime and boostConclusions: Biojector delivery did not improve antibody responses to the rAd5 vaccine compared to needle administration. Homologous boosting with rAd5 gene-based vectors can boost insert-specific antibody responses despite pre-existing vector-specific immunity.Background: Needle-free delivery improves the immunogenicity of DNA vaccines but is also associated with more local reactogenicity. Here we report the first comparison of Biojector and needle administration of a candidate rAd5 HIV vaccine.Methods: Thirty-one adults, 18-55 years, 20 naive and 11 prior rAd5 vaccine recipients were randomized to receive single rAd5 vaccine via needle or Biojector IM injection at 1010 PU in a Phase I open label clinical trial. Solicited reactogenicity was collected for 5 days; clinical safety and immunogenicity follow-up was continued for 24 weeks.

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Homologous boosting with adenoviral serotype 5 HIV Vaccine (rAd5) vector can boost antibody responses despite preexisting vector-specific immunity in a randomized phase I clinical trial

Abstract

ASJC Scopus subject areas

UN SDGs

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