Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa

Walter Jaoko, Etienne Karita, Kayitesi Kayitenkore, Gloria Omosa-Manyonyi, Susan Allen, Soe Than, Elizabeth M. Adams, Barney S. Graham, Richard A. Koup, Robert T. Bailer, Carol Smith, Len Dally, Bashir Farah, Omu Anzala, Claude M. Muvunyi, Jean Bizimana, Tony Tarragona-Fiol, Philip J. Bergin, Peter Hayes Martin Ho, Kelley LoughranWendy Komaroff, Gwynneth Stevens, Helen Thomson, Mark J. Boaz, Josephine H. Cox, Claudia Schmidt, Jill Gilmour, Gary J. Nabel, Patricia Fast, Job Bwayo

Research output: Contribution to journalArticle

Abstract

Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replicationdefective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIVuninfected African adults. Methodology/Principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance: The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was welltolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.

Original languageEnglish (US)
Article numbere12873
Pages (from-to)1-16
Number of pages16
JournalPLoS One
Volume5
Issue number9
DOIs
StatePublished - 2010
Externally publishedYes

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vector vaccines
DNA Vaccines
Adenoviridae
recombinant vaccines
Human immunodeficiency virus 1
HIV-1
Vaccines
immune response
Safety
DNA
Interferon-gamma
HIV Antigens
Adenovirus Vaccines
vaccines
Enzyme-Linked Immunospot Assay
Volunteers
Neutralizing Antibodies
volunteers
Needles
Proteins

ASJC Scopus subject areas

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

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Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa. / Jaoko, Walter; Karita, Etienne; Kayitenkore, Kayitesi; Omosa-Manyonyi, Gloria; Allen, Susan; Than, Soe; Adams, Elizabeth M.; Graham, Barney S.; Koup, Richard A.; Bailer, Robert T.; Smith, Carol; Dally, Len; Farah, Bashir; Anzala, Omu; Muvunyi, Claude M.; Bizimana, Jean; Tarragona-Fiol, Tony; Bergin, Philip J.; Ho, Peter Hayes Martin; Loughran, Kelley; Komaroff, Wendy; Stevens, Gwynneth; Thomson, Helen; Boaz, Mark J.; Cox, Josephine H.; Schmidt, Claudia; Gilmour, Jill; Nabel, Gary J.; Fast, Patricia; Bwayo, Job.

In: PLoS One, Vol. 5, No. 9, e12873, 2010, p. 1-16.

Research output: Contribution to journalArticle

Jaoko, W, Karita, E, Kayitenkore, K, Omosa-Manyonyi, G, Allen, S, Than, S, Adams, EM, Graham, BS, Koup, RA, Bailer, RT, Smith, C, Dally, L, Farah, B, Anzala, O, Muvunyi, CM, Bizimana, J, Tarragona-Fiol, T, Bergin, PJ, Ho, PHM, Loughran, K, Komaroff, W, Stevens, G, Thomson, H, Boaz, MJ, Cox, JH, Schmidt, C, Gilmour, J, Nabel, GJ, Fast, P & Bwayo, J 2010, 'Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa', PLoS One, vol. 5, no. 9, e12873, pp. 1-16. https://doi.org/10.1371/journal.pone.0012873
Jaoko, Walter ; Karita, Etienne ; Kayitenkore, Kayitesi ; Omosa-Manyonyi, Gloria ; Allen, Susan ; Than, Soe ; Adams, Elizabeth M. ; Graham, Barney S. ; Koup, Richard A. ; Bailer, Robert T. ; Smith, Carol ; Dally, Len ; Farah, Bashir ; Anzala, Omu ; Muvunyi, Claude M. ; Bizimana, Jean ; Tarragona-Fiol, Tony ; Bergin, Philip J. ; Ho, Peter Hayes Martin ; Loughran, Kelley ; Komaroff, Wendy ; Stevens, Gwynneth ; Thomson, Helen ; Boaz, Mark J. ; Cox, Josephine H. ; Schmidt, Claudia ; Gilmour, Jill ; Nabel, Gary J. ; Fast, Patricia ; Bwayo, Job. / Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa. In: PLoS One. 2010 ; Vol. 5, No. 9. pp. 1-16.
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abstract = "Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replicationdefective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIVuninfected African adults. Methodology/Principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector{\circledR} 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62{\%} and 86{\%} of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81{\%} of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100{\%} recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance: The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was welltolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.",
author = "Walter Jaoko and Etienne Karita and Kayitesi Kayitenkore and Gloria Omosa-Manyonyi and Susan Allen and Soe Than and Adams, {Elizabeth M.} and Graham, {Barney S.} and Koup, {Richard A.} and Bailer, {Robert T.} and Carol Smith and Len Dally and Bashir Farah and Omu Anzala and Muvunyi, {Claude M.} and Jean Bizimana and Tony Tarragona-Fiol and Bergin, {Philip J.} and Ho, {Peter Hayes Martin} and Kelley Loughran and Wendy Komaroff and Gwynneth Stevens and Helen Thomson and Boaz, {Mark J.} and Cox, {Josephine H.} and Claudia Schmidt and Jill Gilmour and Nabel, {Gary J.} and Patricia Fast and Job Bwayo",
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T1 - Safety and immunogenicity study of multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa

AU - Jaoko, Walter

AU - Karita, Etienne

AU - Kayitenkore, Kayitesi

AU - Omosa-Manyonyi, Gloria

AU - Allen, Susan

AU - Than, Soe

AU - Adams, Elizabeth M.

AU - Graham, Barney S.

AU - Koup, Richard A.

AU - Bailer, Robert T.

AU - Smith, Carol

AU - Dally, Len

AU - Farah, Bashir

AU - Anzala, Omu

AU - Muvunyi, Claude M.

AU - Bizimana, Jean

AU - Tarragona-Fiol, Tony

AU - Bergin, Philip J.

AU - Ho, Peter Hayes Martin

AU - Loughran, Kelley

AU - Komaroff, Wendy

AU - Stevens, Gwynneth

AU - Thomson, Helen

AU - Boaz, Mark J.

AU - Cox, Josephine H.

AU - Schmidt, Claudia

AU - Gilmour, Jill

AU - Nabel, Gary J.

AU - Fast, Patricia

AU - Bwayo, Job

PY - 2010

Y1 - 2010

N2 - Background: We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replicationdefective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIVuninfected African adults. Methodology/Principal Findings: Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×1010 or 1×1011 particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone. Conclusions/Significance: The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was welltolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.

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