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.
| Language | English (US) |
|---|---|
| Article number | e0152038 |
| Journal | PloS one |
| Volume | 11 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2016 |
Fingerprint
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
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: Contribution to journal › Article
}
TY - JOUR
T1 - Comparative immunogenicity of HIV-1 gp140 vaccine delivered by parenteral, and mucosal routes in female volunteers; MUCOVAC2, a randomized two centre study
AU - Cosgrove,Catherine A.
AU - Lacey,Charles J.
AU - Cope,Alethea V.
AU - Bartolf,Angela
AU - Morris,Georgina
AU - Yan,Celine
AU - Baden,Susan
AU - Cole,Tom
AU - Carter,Darrick
AU - Brodnicki,Elizabeth
AU - Shen,Xiaoying
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
AU - McCormack,Sheena
AU - Shattock,Robin J.
PY - 2016/5/1
Y1 - 2016/5/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84969902276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969902276&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0152038
DO - 10.1371/journal.pone.0152038
M3 - Article
VL - 11
JO - PLoS One
T2 - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0152038
ER -