Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study

Catherine A. Cosgrove, Charles J. Lacey, Alethea V. Cope, Angela Bartolf, Georgina Morris, Celine Yan, Susan Baden, Tom Cole, Darrick Carter, Elizabeth Brodnicki, Xiaoying Shen, Sarah Joseph, Stephen C. DeRosa, Lili Peng, Xuesong Yu, Guido Ferrari, Mike Seaman, David C. Montefiori, Nicole Frahm, Georgia D. Tomaras & 3 others Wolfgang Stöhr, Sheena McCormack, Robin J. Shattock

Research output: Research - peer-reviewArticle

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Abstract

Background: Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses. Methods: In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM), intranasal (IN) and intravaginal (IVAG) routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA), IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel. Results: Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization. Conclusions: These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming. Clinical Trials Registration: EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN) Number 11679.

LanguageEnglish (US)
Article numbere0152038
JournalPLoS ONE
Volume11
Issue number5
DOIs
StatePublished - May 1 2016

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Human immunodeficiency virus 1
volunteers
immunization
immune response
vaccines
Volunteers
Immunization
Vaccines
gp140 envelope protein, Human immunodeficiency virus 1
mucosal immunity
antibodies
Mucosal Immunity
Antibodies
clinical trials
Intravaginal Administration
HIV-1
Research
chitosan
neutralization
adjuvants

ASJC Scopus subject areas

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

Cite this

Cosgrove, C. A., Lacey, C. J., Cope, A. V., Bartolf, A., Morris, G., Yan, C., ... Shattock, R. J. (2016). Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study. PLoS ONE, 11(5), [e0152038]. DOI: 10.1371/journal.pone.0152038

Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study. / Cosgrove, Catherine A.; Lacey, Charles J.; Cope, Alethea V.; Bartolf, Angela; Morris, Georgina; Yan, Celine; Baden, Susan; Cole, Tom; Carter, Darrick; Brodnicki, Elizabeth; Shen, Xiaoying; Joseph, Sarah; DeRosa, Stephen C.; Peng, Lili; Yu, Xuesong; Ferrari, Guido; Seaman, Mike; Montefiori, David C.; Frahm, Nicole; Tomaras, Georgia D.; Stöhr, Wolfgang; McCormack, Sheena; Shattock, Robin J.

In: PLoS ONE, Vol. 11, No. 5, e0152038, 01.05.2016.

Research output: Research - peer-reviewArticle

Cosgrove, CA, Lacey, CJ, Cope, AV, Bartolf, A, Morris, G, Yan, C, Baden, S, Cole, T, Carter, D, Brodnicki, E, Shen, X, Joseph, S, DeRosa, SC, Peng, L, Yu, X, Ferrari, G, Seaman, M, Montefiori, DC, Frahm, N, Tomaras, GD, Stöhr, W, McCormack, S & Shattock, RJ 2016, 'Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study' PLoS ONE, vol 11, no. 5, e0152038. DOI: 10.1371/journal.pone.0152038
Cosgrove, Catherine A. ; Lacey, Charles J. ; Cope, Alethea V. ; Bartolf, Angela ; Morris, Georgina ; Yan, Celine ; Baden, Susan ; Cole, Tom ; Carter, Darrick ; Brodnicki, Elizabeth ; Shen, Xiaoying ; Joseph, Sarah ; DeRosa, Stephen C. ; Peng, Lili ; Yu, Xuesong ; Ferrari, Guido ; Seaman, Mike ; Montefiori, David C. ; Frahm, Nicole ; Tomaras, Georgia D. ; Stöhr, Wolfgang ; McCormack, Sheena ; Shattock, Robin J./ Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study. In: PLoS ONE. 2016 ; Vol. 11, No. 5.
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abstract = "Background: Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses. Methods: In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM), intranasal (IN) and intravaginal (IVAG) routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA), IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel. Results: Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization. Conclusions: These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming. Clinical Trials Registration: EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN) Number 11679.",
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AU - Joseph,Sarah

AU - DeRosa,Stephen C.

AU - Peng,Lili

AU - Yu,Xuesong

AU - Ferrari,Guido

AU - Seaman,Mike

AU - Montefiori,David C.

AU - Frahm,Nicole

AU - Tomaras,Georgia D.

AU - Stöhr,Wolfgang

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N2 - Background: Defining optimal routes for induction of mucosal immunity represents an important research priority for the HIV-1 vaccine field. In particular, it remains unclear whether mucosal routes of immunization can improve mucosal immune responses. Methods: In this randomized two center phase I clinical trial we evaluated the systemic and mucosal immune response to a candidate HIV-1 Clade C CN54gp140 envelope glycoprotein vaccine administered by intramuscular (IM), intranasal (IN) and intravaginal (IVAG) routes of administration in HIV negative female volunteers. IM immunizations were co-administered with Glucopyranosyl Lipid Adjuvant (GLA), IN immunizations with 0.5% chitosan and IVAG immunizations were administered in an aqueous gel. Results: Three IM immunizations of CN54 gp140 at either 20 or 100 μg elicited significantly greater systemic and mucosal antibodies than either IN or IVAG immunizations. Following additional intramuscular boosting we observed an anamnestic antibody response in nasally primed subjects. Modest neutralizing responses were detected against closely matched tier 1 clade C virus in the IM groups. Interestingly, the strongest CD4 T-cell responses were detected after IN and not IM immunization. Conclusions: These data show that parenteral immunization elicits systemic and mucosal antibodies in women. Interestingly IN immunization was an effective prime for IM boost, while IVAG administration had no detectable impact on systemic or mucosal responses despite IM priming. Clinical Trials Registration: EudraCT 2010-019103-27 and the UK Clinical Research Network (UKCRN) Number 11679.

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