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Robust vaginal colonization of macaques with a novel vaginally disintegrating
tablet containing a live biotherapeutic product to prevent HIV infection in
women
#MMPMID25875100
Lagenaur LA
; Swedek I
; Lee PP
; Parks TP
PLoS One
2015[]; 10
(4
): e0122730
PMID25875100
show ga
MucoCept is a biotherapeutic for prevention of HIV-1 infection in women and
contains a human, vaginal Lactobacillus jensenii that has been genetically
enhanced to express the HIV-1 entry inhibitor, modified cyanovirin-N (mCV-N). The
objective of this study was to develop a solid vaginal dosage form that supports
sustained vaginal colonization of the MucoCept Lactobacillus at levels previously
shown, with freshly prepared cultures, to protect macaques from SHIV infection
and to test this formulation in a macaque vaginal colonization model. Vaginally
disintegrating tablets were prepared by lyophilizing the formulated bacteria in
tablet-shaped molds, then packaging in foil pouches with desiccant.
Disintegration time, potency and stability of the tablets were assessed. For
colonization, non-synchronized macaques were dosed vaginally with either one
tablet or five tablets delivered over five days. Vaginal samples were obtained at
three, 14, and 21 days post-dosing and cultured to determine Lactobacillus
colonization levels. To confirm identity of the MucoCept Lactobacillus strain,
genomic DNA was extracted from samples on days 14 and 21 and a strain-specific
PCR was performed. Supernatants from bacteria were tested for the presence of the
mCV-N protein by Western blot. The tablets were easy to handle, disintegrated
within two minutes, potent (5.7x1011 CFU/g), and stable at 4°C and 25°C. Vaginal
administration of the tablets to macaques resulted in colonization of the
MucoCept Lactobacillus in 66% of macaques at 14 days post-dosing and 83% after 21
days. There was no significant difference in colonization levels for the one or
five tablet dosing regimens (p=0.88 Day 14, p=0.99 Day 21). Strain-specific PCR
confirmed the presence of the bacteria even in culture-negative macaques.
Finally, the presence of mCV-N protein was confirmed by Western blot analysis
using a specific anti-mCV-N antibody.
|*Organisms, Genetically Modified
[MESH]
|Administration, Intravaginal
[MESH]
|Adult
[MESH]
|Animals
[MESH]
|Bacterial Proteins/*genetics/metabolism
[MESH]
|Carrier Proteins/*genetics/metabolism
[MESH]
|Colony Count, Microbial
[MESH]
|Female
[MESH]
|Gene Expression
[MESH]
|HIV Infections/prevention & control
[MESH]
|HIV-1/drug effects
[MESH]
|Humans
[MESH]
|Lactobacillus/genetics/*growth & development
[MESH]
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