Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection.
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.
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.
Qing
Q
Zhu
James
J
Talton
Guofeng
G
Zhang
Tshaka
T
Cunningham
Zijian
Z
Wang
Robert C
RC
Waters
James
J
Kirk
Bärbel
B
Eppler
Dennis M
DM
Klinman
Yongjun
Y
Sui
Susan
S
Gagnon
Igor M
IM
Belyakov
Russell J
RJ
Mumper
Jay A
JA
Berzofsky
D000276:Adjuvants, Immunologic; D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D018928:Immunity, Mucosal; D007420:Intestine, Large / Q000821:virology; D019344:Lactic Acid; D055666:Lipopeptides; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D053758:Nanoparticles; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D009928:Organ Specificity; D010053:Ovary / Q000821:virology; D011070:Poly I-C; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011109:Polymethacrylic Acids; D012007:Rectum / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control*; D014616:Vaccinia virus / Q000276:immunology* / Q000302:isolation & purification; D014621:Vagina / Q000276:immunology*; D019562:Viral Load; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; C583869:CpG ODN 1466; C583868:CpG ODN 1555; D055666:Lipopeptides; D009838:Oligodeoxyribonucleotides; D011109:Polymethacrylic Acids; D022223:Vaccines, Subunit; D014765:Viral Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C106335:macrophage stimulatory lipopeptide 2; D011070:Poly I-C