Induction of mucosal and systemic immune responses following oral immunization of mice with Lactococcus lactis expressing human papillomavirus type 16 L1

Vaccine ◽  
2007 ◽  
Vol 25 (47) ◽  
pp. 8049-8057 ◽  
Author(s):  
Hee-Jeong Cho ◽  
Hye-Jeong Shin ◽  
In-Kwon Han ◽  
Woon-Won Jung ◽  
Young Bong Kim ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Immune Responses ◽  
Lactococcus Lactis ◽  
Oral Immunization ◽  
Human Papillomavirus Type 16

Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Ke-Qin Xin ◽  
Yuka Hoshino ◽  
Yoshihiko Toda ◽  
Shizunobu Igimi ◽  
Yoshitsugu Kojima ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lactococcus Lactis ◽  
Potential Role ◽  
Protective Efficacy ◽  
Oral Immunization ◽  
Vaccine Strategy ◽  
Regional Lymph Nodes ◽  
Viral Loads ◽  
Recombinant Lactococcus Lactis ◽  
Further Development

Abstract This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

scholarly journals Immune Responses and Therapeutic Antitumor Effects of an Experimental DNA Vaccine Encoding Human Papillomavirus Type 16 Oncoproteins Genetically Fused to Herpesvirus Glycoprotein D

2010 ◽  
Vol 17 (10) ◽  
pp. 1576-1583 ◽  
Author(s):  
Mariana O. Diniz ◽  
Marcio O. Lasaro ◽  
Hildegund C. Ertl ◽  
Luís C. S. Ferreira
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
Immune Responses ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Glycoprotein D ◽  
Antitumor Effects ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8+ T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells). In the present report, we characterized some previously uncovered aspects concerning the induction of CD8+ T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells. Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4+ T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8+ T-cell responses. In addition, we determined the priming/boosting properties of pgD-E7E6E5 when used in combination with a recombinant serotype 68 adenovirus (AdC68) vector encoding the same chimeric antigen. Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8+ T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2Db -restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein. Up to 70% of the mice challenged with 5 × 105 TC-1 cells and immunized with pgD-E7E6E5 controlled tumor development even after 3 days of tumor cell challenge. In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells. In conclusion, the present results expand our previous knowledge on the immune modulation properties of the pgD-E7E6E5 vector and demonstrate, for the first time, the strong antitumor effects of the DNA vaccine, raising promising perspectives regarding the development of immunotherapeutic reagents for the control of HPV-16-associated tumors.

scholarly journals Trachea, Lung, and Tracheobronchial Lymph Nodes Are the Major Sites Where Antigen-Presenting Cells Are Detected after Nasal Vaccination of Mice with Human Papillomavirus Type 16 Virus-Like Particles

2002 ◽  
Vol 76 (24) ◽  
pp. 12596-12602 ◽  
Author(s):  
Carole Balmelli ◽  
Stéphane Demotz ◽  
Hans Acha-Orbea ◽  
Pierre De Grandi ◽  
Denise Nardelli-Haefliger
Keyword(s):  
Immune Response ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Lymph Nodes ◽  
Lymphoid Tissue ◽  
Lower Respiratory Tract ◽  
Human Papillomavirus Type 16 ◽  
Nasal Vaccination ◽  
Antigen Presenting

ABSTRACT Vaccination by the nasal route has been successfully used for the induction of immune responses. Either the nasal-associated lymphoid tissue (NALT), the bronchus-associated lymphoid tissue, or lung dendritic cells have been mainly involved. Following nasal vaccination of mice with human papillomavirus type 16 (HPV16) virus-like-particles (VLPs), we have previously shown that interaction of the antigen with the lower respiratory tract was necessary to induce high titers of neutralizing antibodies in genital secretions. However, following a parenteral priming, nasal vaccination with HPV16 VLPs did not require interaction with the lung to induce a mucosal immune response. To evaluate the contribution of the upper and lower respiratory tissues and associated lymph nodes (LN) in the induction of humoral responses against HPV16 VLPs after nasal vaccination, we localized the immune inductive sites and identified the antigen-presenting cells involved using a specific CD4+ T-cell hybridoma. Our results show that the trachea, the lung, and the tracheobronchial LN were the major sites responsible for the induction of the immune response against HPV16 VLP, while the NALT only played a minor role. Altogether, our data suggest that vaccination strategies aiming to induce efficient immune responses against HPV16 VLP in the female genital tract should target the lower respiratory tract.

scholarly journals A Direct Comparison of Human Papillomavirus Type 16 L1 Particles Reveals a Lower Immunogenicity of Capsomeres than Viruslike Particles with Respect to the Induced Antibody Response

2008 ◽  
Vol 82 (11) ◽  
pp. 5472-5485 ◽  
Author(s):  
Nadja Thönes ◽  
Anna Herreiner ◽  
Lysann Schädlich ◽  
Konrad Piuko ◽  
Martin Müller
Keyword(s):  
Human Papillomavirus ◽  
Oral Immunization ◽  
Immunoglobulin M ◽  
Toll Like Receptor 4 ◽  
Humoral Immune ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses ◽  
Adjuvant System ◽  
Antibody Titers ◽  
Viruslike Particles

ABSTRACT Capsomeres are considered to be an alternative to viruslike particle (VLP)-based vaccines as they can be produced in prokaryotic expression systems. So far, no detailed side-by-side comparison of VLPs and capsomeres has been performed. In the present study, we immunized mice with insect cell-derived human papillomavirus type 16 VLPs and capsomeres. VLPs induced consistently higher antibody titers than capsomeres but the two forms induced similar CD8 T-cell responses after subcutaneous, intranasal, and oral immunization, and at least 20 to 40 times more L1 in the form of capsomeres than in the form of VLPs was needed to achieve comparable antibody responses. These results were confirmed by DNA immunization. The lower immunogenicity of capsomeres was independent of the isotype switch, as it was also observed for the early immunoglobulin M responses. Although there were differences in the display of surface epitopes between the L1 particles, these did not contribute significantly to the differences in the immune responses. capsomeres were less immunogenic than VLPs in Toll-like receptor 4 (TLR4)-deficient mice, suggesting that the lower immunogenicity is not due to a failure of capsomeres to trigger TLR4. We observed better correlation between antibody results from enzyme-linked immunosorbent assays and neutralization assays for sera from VLP-immunized mice than for sera from capsomere-immunized mice, suggesting qualitative differences between VLPs and capsomeres. We also showed that the lower immunogenicity of capsomeres could be compensated by the use of an adjuvant system containing MPL. Taken together, these results suggest that, presumably because of the lower degree of complexity of the antigen organization, capsomeres are significantly less immunogenic than VLPs with respect to the humoral immune response and that this characteristic should be considered in the design of putative capsomere-based prophylactic vaccines.

Sign in / Sign up

Export Citation Format

Share Document