Cranage, MP

de Stegmann, DS Miranda

Klein, K

Mann, JF

McKay, PF

Shattock, RJ

Stieh, D

English

PubMed

JF Mann

DS de Stegmann

K Klein

D Stieh

MP Cranage

RJ Shattock

PF McKay

Springer - Publisher Connector

P11-09. Mucosal vaccination with a transferrin-gp140 conjugate via the nasal but not vaginal route elicits robust systemic and vaginal IgG and IgA responses

DS Miranda de Stegmann

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BioMed Central
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Retrovirology
Open AccessPoster presentation
P11-09. Mucosal vaccination with a transferrin-gp140 conjugate via 
the nasal but not vaginal route elicits robust systemic and vaginal 
IgG and IgA responses
JF Mann*, DS Miranda de Stegmann, K Klein, D Stieh, MP Cranage, 
RJ Shattock and PF McKay
Address: Infectious Diseases, SGUL, London, UK
* Corresponding author    
Background
Mucosal anti-HIV immunity at the virus portal of entry is
likely essential to protect against sexual transmission of
HIV. While the female genital tract has some immune-
inductive potential, responses elicited to vaccine antigens
applied to the vaginal mucosae have been modest at best.
Immunological linkage between nasal and vaginal MALT
has been demonstrated in both mouse and man, suggest-
ing that nasal vaccination may promote vaginal mucosal
immunity. We used a novel transferrin receptor targeted
vaccine conjugate to enhance delivery of a vaccinating
antigen across the mucosal epithelial barrier and com-
pared nasal with vaginal vaccination.
Methods
We conjugated trimeric Clade C HIV-gp140 to human
transferrin (Tf) using a streptavidin-biotin linkage. Conju-
gate formation was characterized by SDS-PAGE and size
analysis then topically administered nasally or vaginally
to medroxyprogesterone-treated mice with or without
previous unadjuvanted gp140 systemic priming. Serum
and vaginal lavage samples were collected and tested by
ELISA for anti-HIV-gp140 specific IgG and IgA.
Results
Unconjugated HIV-gp140 administered to either the vag-
inal or nasal mucosa was insufficient to generate antigen-
specific responses. However, the Tf-gp140 conjugate elic-
ited antigen-specific IgG responses in serum after nasal
administration. A systemic prime followed by either a vag-
inal or nasal mucosal boost vaccination significantly
enhanced antigen-specific serum IgG, with the Tf-gp140
conjugate being more effective than antigen alone. Impor-
tantly, a systemic gp140 priming vaccination followed by
nasal Tf-gp140 conjugate boosts generated robust gp140-
specific vaginal mucosal IgG and IgA antibody responses.
Conclusion
The comparison of the utility of nasal or vaginal mucosae
as immune-inductive sites demonstrated that vaccination
via the nasal but not the vaginal route elicited strong vag-
inal IgG and IgA responses. Our novel conjugate, that
delivers vaccine antigens by transcytosis to sub-mucosal
compartments where immune cells reside, highlighted
the difference between the immune-inductive potential of
these two mucosal sites.
from AIDS Vaccine 2009
Paris, France. 19–22 October 2009
Published: 22 October 2009
Retrovirology 2009, 6(Suppl 3):P154 doi:10.1186/1742-4690-6-S3-P154
<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>
This abstract is available from: http://www.retrovirology.com/content/6/S3/P154
© 2009 Mann et al; licensee BioMed Central Ltd. 


Shattock RJ

Cranage MP

Stieh D

Klein K

de Stegmann DS

Mann JF

McKay PF

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P11-09. Mucosal vaccination with a transferrin-gp140 conjugate via the nasal but not vaginal route elicits robust systemic and vaginal IgG and IgA responses

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