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Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses.

Curran RM, Donnelly L, Morrow RJ, Fraser C, Andrews G, Cranage M, Malcolm RK, Shattock RJ, Woolfson AD - Vaccine (2009)

Bottom Line: CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24h.Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions.The RSVs are a viable delivery modality for vaginal immunization.

View Article: PubMed Central - PubMed

Affiliation: The School of Pharmacy, The Queen's University of Belfast, Belfast, BT9 7BL, Northern Ireland, UK. rhonda.curran@qub.ac.uk

ABSTRACT
Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix-forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24h. Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions. The RSVs are a viable delivery modality for vaginal immunization.

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Intravaginal immunization of rabbits with CN54gp140 formulated in 3% RSV (a) or 5% RSV stimulated production of systemic IgG anti-gp140 antibody. IgG (●) and IgA (▴) gp-140-specific ELISA titres were determined by dilution to a standardized end-point and the limits of detection are shown for IgG () and IgA ().
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fig3: Intravaginal immunization of rabbits with CN54gp140 formulated in 3% RSV (a) or 5% RSV stimulated production of systemic IgG anti-gp140 antibody. IgG (●) and IgA (▴) gp-140-specific ELISA titres were determined by dilution to a standardized end-point and the limits of detection are shown for IgG () and IgA ().

Mentions: Five of six rabbits receiving CN54gp140 antigen formulated in 3% RSV gel and 5 of 6 animals receiving antigen formulated in 5% RSV gel had evidence of specific antibody responses detectable in serum (Fig. 3) and in secretions from the female genital tract (Table 2). Serum IgG antibody was detected as early as day 13 in 1 of the animals receiving 3% RSV and in 3 of 6 animals receiving 5% RSV with titres ranging from 130 to 320. By day 20, the last day of the study, IgG antibody titres had increased in all these animals and another 6 animals had sero-converted, although in two animals, one from each group, titres only just reached the minimum detectable. Overall, serum IgG antibody titres ranged from 100 to 1500 at day 20. Titres were broadly similar between the two groups (100–1280 and 100–1500 for each group respectively). IgA antibody was undetectable in any serum sample at or above the minimum titre of 10.


Vaginal delivery of the recombinant HIV-1 clade-C trimeric gp140 envelope protein CN54gp140 within novel rheologically structured vehicles elicits specific immune responses.

Curran RM, Donnelly L, Morrow RJ, Fraser C, Andrews G, Cranage M, Malcolm RK, Shattock RJ, Woolfson AD - Vaccine (2009)

Intravaginal immunization of rabbits with CN54gp140 formulated in 3% RSV (a) or 5% RSV stimulated production of systemic IgG anti-gp140 antibody. IgG (●) and IgA (▴) gp-140-specific ELISA titres were determined by dilution to a standardized end-point and the limits of detection are shown for IgG () and IgA ().
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2824087&req=5

fig3: Intravaginal immunization of rabbits with CN54gp140 formulated in 3% RSV (a) or 5% RSV stimulated production of systemic IgG anti-gp140 antibody. IgG (●) and IgA (▴) gp-140-specific ELISA titres were determined by dilution to a standardized end-point and the limits of detection are shown for IgG () and IgA ().
Mentions: Five of six rabbits receiving CN54gp140 antigen formulated in 3% RSV gel and 5 of 6 animals receiving antigen formulated in 5% RSV gel had evidence of specific antibody responses detectable in serum (Fig. 3) and in secretions from the female genital tract (Table 2). Serum IgG antibody was detected as early as day 13 in 1 of the animals receiving 3% RSV and in 3 of 6 animals receiving 5% RSV with titres ranging from 130 to 320. By day 20, the last day of the study, IgG antibody titres had increased in all these animals and another 6 animals had sero-converted, although in two animals, one from each group, titres only just reached the minimum detectable. Overall, serum IgG antibody titres ranged from 100 to 1500 at day 20. Titres were broadly similar between the two groups (100–1280 and 100–1500 for each group respectively). IgA antibody was undetectable in any serum sample at or above the minimum titre of 10.

Bottom Line: CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24h.Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions.The RSVs are a viable delivery modality for vaginal immunization.

View Article: PubMed Central - PubMed

Affiliation: The School of Pharmacy, The Queen's University of Belfast, Belfast, BT9 7BL, Northern Ireland, UK. rhonda.curran@qub.ac.uk

ABSTRACT
Rheologically structured vehicle (RSV) gels were developed as delivery systems for vaginal mucosal vaccination with an HIV-1 envelope glycoprotein (CN54gp140). RSVs comprised a mucoadhesive matrix-forming and vaginal fluid absorbing polymer. The mucoadhesive and rheological properties of the RSVs were evaluated in vitro, and the distribution, antigenicity and release of CN54gp140 were analysed by ELISA. CN54gp140 was uniformly distributed within the RSVs and continuously released in vitro in an antigenically intact form over 24h. Vaginal administration to rabbits induced specific serum IgG, and IgG and IgA in genital tract secretions. The RSVs are a viable delivery modality for vaginal immunization.

Show MeSH