Chlamydia trachomatis recombinant MOMP encapsulated in PLGA nanoparticles triggers primarily T helper 1 cellular and antibody immune responses in mice: a desirable candidate nanovaccine

被引:47
作者
Fairley, Stacie J. [1 ]
Singh, Shree R. [1 ]
Yilma, Abebayehu N. [1 ]
Waffo, Alain B. [1 ]
Subbarayan, Praseetha [1 ]
Dixit, Saurabh [1 ]
Taha, Murtada A. [1 ]
Cambridge, Chino D. [1 ]
Dennis, Vida A. [1 ]
机构
[1] Alabama State Univ, Ctr NanoBiotechnol Res, Montgomery, AL 36104 USA
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2013年 / 8卷
基金
美国国家科学基金会;
关键词
Chlamydia trachomatis; bacteria; vaccine; antibody; cytokines; PLGA nanoparticles; OUTER-MEMBRANE PROTEIN; GENITAL-TRACT INFECTION; PROTECTIVE IMMUNITY; INDUCE PROTECTION; SUSTAINED-RELEASE; CHOLERA-TOXIN; T-CELLS; IMMUNIZATION; VACCINE; LIVE;
D O I
10.2147/IJN.S44155
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
We recently demonstrated by in vitro experiments that PLGA (poly D, L-lactide-co-glycolide) potentiates T helper 1 (Th1) immune responses induced by a peptide derived from the recombinant major outer membrane protein (rMOMP) of Chlamydia trachomatis, and may be a promising vaccine delivery system. Herein we evaluated the immune-potentiating potential of PLGA by encapsulating the full-length rMOMP (PLGA-rMOMP), characterizing it in vitro, and investigating its immunogenicity in vivo. Our hypothesis was that PLGA-rMOMP triggers Th1 immune responses in mice, which are desirable prerequisites for a C. trachomatis candidate nanovaccine. Physical-structural characterizations of PLGA-rMOMP revealed its size (approximately 272 nm), zeta potential (-14.30 mV), apparent spherical smooth morphology, and continuous slow release pattern. PLGA potentiated the ability of encapsulated rMOMP to trigger production of cytokines and chemokines by mouse J774 macrophages. Flow cytometric analyses revealed that spleen cells from BALB/c mice immunized with PLGA-rMOMP had elevated numbers of CD4+ and CD8+ T cell subsets, and secreted more rMOMP-specific interferon-gamma (Th1) and interleukin (IL)-12p40 (Th1/Th17) than IL-4 and IL-10 (Th2) cytokines. PLGA-rMOMP-immunized mice produced higher serum immunoglobulin (Ig)G and IgG2a (Th1) than IgG1 (Th2) rMOMP-specific antibodies. Notably, sera from PLGA-rMOMP-immunized mice had a 64-fold higher Th1 than Th2 antibody titer, whereas mice immunized with rMOMP in Freund's adjuvant had only a four-fold higher Th1 than Th2 antibody titer, suggesting primarily induction of a Th1 antibody response in PLGA-rMOMP-immunized mice. Our data underscore PLGA as an effective delivery system for a C. trachomatis vaccine. The capacity of PLGA-rMOMP to trigger primarily Th1 immune responses in mice promotes it as a highly desirable candidate nanovaccine against C. trachomatis.
引用
收藏
页码:2085 / 2099
页数:15
相关论文
共 69 条
  • [31] Sustained release of recombinant human insulin-like growth factor-I for treatment of diabetes
    Lam, XM
    Duenas, ET
    Daugherty, AL
    Levin, N
    Cleland, JL
    [J]. JOURNAL OF CONTROLLED RELEASE, 2000, 67 (2-3) : 281 - 292
  • [32] Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system
    Lima, KM
    Júnior, JMR
    [J]. BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH, 1999, 32 (02) : 171 - 180
  • [33] Vaccination against chlamydial infections of man and animals
    Longbottom, D
    Livingstone, M
    [J]. VETERINARY JOURNAL, 2006, 171 (02) : 263 - 275
  • [34] Lu H, 1999, INFECT IMMUN, V67, P1763
  • [35] Duration of Untreated Chlamydial Genital Infection and Factors Associated with Clearance: Review of Animal Studies
    Miyairi, Isao
    Ramsey, Kyle H.
    Patton, Dorothy L.
    [J]. JOURNAL OF INFECTIOUS DISEASES, 2010, 201 : S96 - S103
  • [36] Microencapsulation of rh-erythropoietin, using biodegradable poly(D,L-lactide-co-glycolide): Protein stability and the effects of stabilizing excipients
    Morlock, M
    Koll, H
    Winter, G
    Kissel, T
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 1997, 43 (01) : 29 - 36
  • [37] Nano/micro technologies for delivering macromolecular therapeutics using poly(D,L-lactide-co-glycolide) and its derivatives
    Mundargi, Raghavendra C.
    Babu, V. Ramesh
    Rangaswamy, Vidhya
    Patel, Pradip
    Aminabhavi, Tejraj M.
    [J]. JOURNAL OF CONTROLLED RELEASE, 2008, 125 (03) : 193 - 209
  • [38] Epidemiology of female genital Chlamydia trachomatis infections
    Norman, J
    [J]. BEST PRACTICE & RESEARCH IN CLINICAL OBSTETRICS & GYNAECOLOGY, 2002, 16 (06): : 775 - 787
  • [39] Ortiz L, 1996, J IMMUNOL, V157, P4554
  • [40] Immunization with the Chlamydia trachomatis major outer membrane protein, using adjuvants developed for human vaccines, can induce partial protection in a mouse model against a genital challenge
    Pal, S
    Peterson, EM
    Rappuoli, R
    Ratti, G
    de la Maza, LM
    [J]. VACCINE, 2006, 24 (06) : 766 - 775