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Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.

Zhu Q, Talton J, Zhang G, Cunningham T, Wang Z, Waters RC, Kirk J, Eppler B, Klinman DM, Sui Y, Gagnon S, Belyakov IM, Mumper RJ, Berzofsky JA - Nat. Med. (2012)

Bottom Line: Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract.Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system.Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

View Article: PubMed Central - PubMed

Affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA; Department of Oncology, Air Force General Hospital, Beijing, China.

ABSTRACT
Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

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Related in: MedlinePlus

Orally delivered FS30D-coated PLGA nanoparticle peptide vaccine confers T-cell mediated resistance to virus infection in the rectal or vaginal tract. FS30D/PLGA/PeptAg+TLRL or L100-55/PLGA/PeptAg+TLRL was given orally to mice twice with a two-week interval, followed by i.c.r. (a) or i.vag. (b) challenge with 2×107 or 1×107 PFU of vPE16, respectively, three weeks after the last immunization. Ovaries (where this virus primarily replicates) were removed at day 6 for viral titer assessment. **P < 0.01, ***P < 0.001 indicate the significant difference in viral titer between the group with asterisks and each of the groups without asterisks (n = 12 15 per group).
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Figure 3: Orally delivered FS30D-coated PLGA nanoparticle peptide vaccine confers T-cell mediated resistance to virus infection in the rectal or vaginal tract. FS30D/PLGA/PeptAg+TLRL or L100-55/PLGA/PeptAg+TLRL was given orally to mice twice with a two-week interval, followed by i.c.r. (a) or i.vag. (b) challenge with 2×107 or 1×107 PFU of vPE16, respectively, three weeks after the last immunization. Ovaries (where this virus primarily replicates) were removed at day 6 for viral titer assessment. **P < 0.01, ***P < 0.001 indicate the significant difference in viral titer between the group with asterisks and each of the groups without asterisks (n = 12 15 per group).

Mentions: To evaluate the protective efficacy of this vaccine, after prime and boost oral immunization, we challenged mice rectally with a replication-competent vaccinia virus vPE-16, which expresses the HIV Env epitope P18-I10 used in the peptide vaccine. Mice immunized with the L100-55-coated vaccine were not protected from the virus challenge. However, the FS30D-coated vaccine reduced viral load almost equally as well as the peptide vaccine given i.c.r. (Fig. 3a). Therefore, oral delivery of FS30D-coated PLGA vaccine targeting the large intestine is effective for local colorectal vaccination against viral infection.


Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.

Zhu Q, Talton J, Zhang G, Cunningham T, Wang Z, Waters RC, Kirk J, Eppler B, Klinman DM, Sui Y, Gagnon S, Belyakov IM, Mumper RJ, Berzofsky JA - Nat. Med. (2012)

Orally delivered FS30D-coated PLGA nanoparticle peptide vaccine confers T-cell mediated resistance to virus infection in the rectal or vaginal tract. FS30D/PLGA/PeptAg+TLRL or L100-55/PLGA/PeptAg+TLRL was given orally to mice twice with a two-week interval, followed by i.c.r. (a) or i.vag. (b) challenge with 2×107 or 1×107 PFU of vPE16, respectively, three weeks after the last immunization. Ovaries (where this virus primarily replicates) were removed at day 6 for viral titer assessment. **P < 0.01, ***P < 0.001 indicate the significant difference in viral titer between the group with asterisks and each of the groups without asterisks (n = 12 15 per group).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475749&req=5

Figure 3: Orally delivered FS30D-coated PLGA nanoparticle peptide vaccine confers T-cell mediated resistance to virus infection in the rectal or vaginal tract. FS30D/PLGA/PeptAg+TLRL or L100-55/PLGA/PeptAg+TLRL was given orally to mice twice with a two-week interval, followed by i.c.r. (a) or i.vag. (b) challenge with 2×107 or 1×107 PFU of vPE16, respectively, three weeks after the last immunization. Ovaries (where this virus primarily replicates) were removed at day 6 for viral titer assessment. **P < 0.01, ***P < 0.001 indicate the significant difference in viral titer between the group with asterisks and each of the groups without asterisks (n = 12 15 per group).
Mentions: To evaluate the protective efficacy of this vaccine, after prime and boost oral immunization, we challenged mice rectally with a replication-competent vaccinia virus vPE-16, which expresses the HIV Env epitope P18-I10 used in the peptide vaccine. Mice immunized with the L100-55-coated vaccine were not protected from the virus challenge. However, the FS30D-coated vaccine reduced viral load almost equally as well as the peptide vaccine given i.c.r. (Fig. 3a). Therefore, oral delivery of FS30D-coated PLGA vaccine targeting the large intestine is effective for local colorectal vaccination against viral infection.

Bottom Line: Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract.Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system.Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

View Article: PubMed Central - PubMed

Affiliation: Vaccine Branch, Center for Cancer Research, National Cancer Institute, US National Institutes of Health, Bethesda, Maryland, USA; Department of Oncology, Air Force General Hospital, Beijing, China.

ABSTRACT
Both rectal and vaginal mucosal surfaces serve as transmission routes for pathogenic microorganisms. Vaccination through large intestinal mucosa, previously proven protective for both of these mucosal sites in animal studies, can be achieved successfully by direct intracolorectal (i.c.r.) administration, but this route is clinically impractical. Oral vaccine delivery seems preferable but runs the risk of the vaccine's destruction in the upper gastrointestinal tract. Therefore, we designed a large intestine-targeted oral delivery with pH-dependent microparticles containing vaccine nanoparticles, which induced colorectal immunity in mice comparably to colorectal vaccination and protected against rectal and vaginal viral challenge. Conversely, vaccine targeted to the small intestine induced only small intestinal immunity and provided no rectal or vaginal protection, demonstrating functional compartmentalization within the gut mucosal immune system. Therefore, using this oral vaccine delivery system to target the large intestine, but not the small intestine, may represent a feasible new strategy for immune protection of rectal and vaginal mucosa.

Show MeSH
Related in: MedlinePlus