scholarly journals Mucosal Administration of CpG Oligodeoxynucleotide Elicits Strong CC and CXC Chemokine Responses in the Vagina and Serves as a Potent Th1-Tilting Adjuvant for Recombinant gD2 Protein Vaccination against Genital Herpes

2006 ◽  
Vol 80 (11) ◽  
pp. 5283-5291 ◽  
Author(s):  
Sara Tengvall ◽  
Annika Lundqvist ◽  
Roselyn J. Eisenberg ◽  
Gary H. Cohen ◽  
Ali M. Harandi

ABSTRACT Although sexually transmitted pathogens are capable of inducing pathogen-specific immune responses, vaginal administration of nonreplicating antigens elicits only weak, nondisseminating immune responses. The present study was undertaken to examine the potential of CpG-containing oligodeoxynucleotide (CpG ODN) for induction of chemokine responses in the genital tract mucosa and also as a vaginal adjuvant in combination with glycoprotein D of herpes simplex virus type 2 (HSV-2) for induction of antigen-specific immune responses. We found that a single intravaginal administration of CpG ODN in mice stimulates a rapid and potent response of CC chemokines macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and RANTES as well as of CXC chemokines MIP-2 and IP-10 in the vagina and/or the genital lymph nodes. Importantly, intravaginal vaccination with recombinant gD2 in combination with CpG ODN gave rise to a strong antigen-specific Th1-like immune response in the genital lymph nodes as well as the spleens of the vaccinated mice. Further, such an immunization scheme conferred both systemic and mucosal immunoglobulin G antibody responses as well as protection against an otherwise lethal vaginal challenge with HSV-2. These results illustrate the potential of CpG ODN for induction of potent chemokine responses in the genital tract and also as a vaginal adjuvant for generation of Th1-type mucosal and systemic immune responses towards a nonreplicating antigen derived from a sexually transmitted pathogen. These data have implications for the development of a mucosal vaccine against genital herpes and possibly other sexually transmitted diseases.

2009 ◽  
Vol 17 (1) ◽  
pp. 23-35 ◽  
Author(s):  
John W. Mapletoft ◽  
Laura Latimer ◽  
Lorne A. Babiuk ◽  
Sylvia van Drunen Littel-van den Hurk

ABSTRACT Bovine respiratory syncytial virus (BRSV) infects cells of the respiratory mucosa, so it is desirable to develop a vaccination strategy that induces mucosal immunity. To achieve this, various delivery routes were compared for formalin-inactivated (FI) BRSV formulated with CpG oligodeoxynucleotide (ODN) and polyphosphazene (PP). Intranasal delivery of the FI-BRSV formulation was superior to subcutaneous delivery in terms of antibody, cell-mediated, and mucosal immune responses, as well as reduction in virus replication after BRSV challenge. Although intranasal delivery of FI-BRSV also induced higher serum and lung antibody titers and gamma interferon (IFN-γ) production in the lungs than intranasal-subcutaneous and/or subcutaneous-intranasal prime-boost strategies, no significant differences were observed in cell-mediated immune responses or virus replication in the lungs of challenged mice. Interleukin 5 (IL-5), eotaxin, and eosinophilia were enhanced after BRSV challenge in the lungs of subcutaneously immunized mice compared to unvaccinated mice, but not in the lungs of mice immunized intranasally or through combinations of the intranasal and subcutaneous routes. These results suggest that two intranasal immunizations with FI-BRSV formulated with CpG ODN and PP are effective and safe as an approach to induce systemic and mucosal responses, as well to reduce virus replication after BRSV challenge. Furthermore, intranasal-subcutaneous and subcutaneous-intranasal prime-boost strategies were also safe and almost as efficacious. In addition to the implications for the development of a protective BRSV vaccine for cattle, formulation with CpG ODN and PP could also prove important in the development of a mucosal vaccine that induces protective immunity against human RSV.


1996 ◽  
Vol 7 (4) ◽  
pp. 229-232 ◽  
Author(s):  
S E Barton ◽  
P E Munday ◽  
R J Patel

A frequent component of the management of patients with genital herpes concerns the possibility of asymptomatic shedding and potential sexual transmission of the virus. Approaches intended to provide supportive counselling and reassurance of patients about these issues need now to be modified in the light of increasing data of the frequency of asymptomatic detection of virus and the effects of antiviral therapy on this phenomenon. Further studies to delineate the relationship between asymptomatic detection of HSV in the genital tract and the mechanism of sexual transmission of this virus need to be conducted before clinicians instigate antiviral suppressive treatment primarily to prevent sexual transmission of HSV. However, it is important that the new data and our greater understanding of the natural history of genital herpes is translated into accurate and comprehensible information for our patients.


2021 ◽  
pp. 263207702110492
Author(s):  
Stephanie I. V. Cazeau-Bandoo ◽  
Ivy K. Ho

The sexual health of Black women has been compromised by racial and discriminatory healthcare practices from slavery through current medical and institutional barriers to care. This paper proposes a conceptual framework that identifies the link between stigma, gendered racism, and historical underpinnings that contribute to ineffective healthcare utilization of Black women diagnosed with the chronic sexually transmitted infection (STI), genital herpes. This paper also draws attention to different social factors that act as barriers to effective healthcare utilization and influence the health outcomes of Black women beyond individual factors. Using a socio-ecological framework, this paper reviews multi-level (i.e., individual, interpersonal, community, and institutional/policy) influences of the experience of genital herpes among Black women. Recommendations are provided to improve the ability of health systems and medical providers to deliver appropriate services to diverse populations, thereby improving healthcare utilization and reducing disparities for Black women.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Achchhe L. Patel ◽  
Prashant K. Mishra ◽  
Divya Sachdev ◽  
Uma Chaudhary ◽  
Dorothy L. Patton ◽  
...  

Chlamydia trachomatis(CT) is an important cause of sexually transmitted genital tract infections (STIs) and trachoma. Despite major research into chlamydial pathogenesis and host immune responses, immunoprotection has been hampered by the incomplete understanding of protective immunity in the genital tract. Characterized vaccine candidates have shown variable efficacy ranging from no protection to partial protectionin vivo. It is therefore a research priority to identify novel chlamydial antigens that may elicit protective immune responses against CT infection. In the present study we assessed the seroprevalence of antibodies against protein kinase1 (Pkn1), DNA ligaseA (LigA), and major outer membrane protein A (OmpA) following natural CT infection in humans and in experimentally induced CT infection inMacaca nemestrina. Antigenic stretches of Pkn1, LigA, and OmpA were identified using bioinformatic tools.Pkn1,LigA, andOmpAgenes were cloned in bacterial expression vector and purified by affinity chromatography. Our results demonstrate significantly high seroprevalence of antibodies against purified Pkn1 and OmpA in sera obtained from the macaque animal model and human patients infected with CT. In contrast no significant seroreactivity was observed for LigA. The seroprevalence of antibodies against Pkn1 suggest that nonsurface chlamydial proteins could also be important for developing vaccines forC. trachomatis.


2007 ◽  
Vol 75 (10) ◽  
pp. 4917-4922 ◽  
Author(s):  
Catherine P. A. Ivory ◽  
Kris Chadee

ABSTRACT The development of an effective amebiasis vaccine could improve child health in the developing world, reducing cases of amebic colitis and liver abscess. An ideal vaccine would be comprised of a well-characterized parasite antigen and an adjuvant, which would have high potency while driving the immune response in a Th1 direction. This study describes a mucosal vaccine composed of the Entamoeba histolytica galactose/N-acetyl-d-galactosamine-inhibitable lectin (Gal-lectin) and CpG oligodeoxynucleotides (CpG-ODN). The Gal-lectin is a protein involved in parasite virulence and adherence and is known to activate immune cells, while CpG-ODN are known to be potent inducers of type 1-like immune responses. We demonstrated that intranasal administration of the vaccine resulted in strong Gal-lectin-specific Th1 responses and humoral responses. Vaccination induced the production of Gal-lectin-specific T cells and the production of the proinflammatory cytokine gamma interferon. Vaccinated animals had detectable serum anti-Gal-lectin immunoglobulin G (IgG) and stool anti-Gal-lectin IgA capable of blocking parasite adherence to target cells in vitro. One week after immunization, gerbils were challenged intrahepatically with live trophozoites. Vaccinated gerbils had no detectable abscesses after day 5, whereas control gerbils developed larger abscesses. These results show that mucosal vaccination with Gal-lectin and CpG-ODN can induce both systemic and humoral immune responses.


2005 ◽  
Vol 79 (23) ◽  
pp. 14632-14639 ◽  
Author(s):  
Kevin C. Yim ◽  
Clifford J. Carroll ◽  
Ana Tuyama ◽  
Natalia Cheshenko ◽  
Maria Josefina Carlucci ◽  
...  

ABSTRACT Prevention of genital herpes and other sexually transmitted infections (STI) is a critical health priority because of the overwhelming impact on women and infants and the epidemiological association with human immunodeficiency virus (HIV)/AIDS. Small animal models are essential for evaluating strategies for prevention or treatment of STI. Neither the murine nor the guinea pig model of genital herpes fully recapitulates human disease. We demonstrate that herpes simplex virus type 2 (HSV-2) readily infects inbred cotton rats (Sigmodon hispidus). Consistent infection does not require pretreatment with medroxyprogesterone, and primary disease resembles that observed in humans. The animals develop genital lesions and fully recover. During primary infection, viral DNA is also detected in liver, lungs, brain, and kidneys. Clinical self-limited recurrences occur spontaneously but may also be induced by dexamethasone. Pretreatment of cotton rats with PRO 2000 gel, a candidate vaginal microbicide being evaluated in clinical trials to prevent HSV and HIV, protects cotton rats from HSV. Together, these studies suggest that the cotton rat may provide an excellent model to study genital herpes and to evaluate preventive strategies.


1993 ◽  
Vol 23 (2) ◽  
pp. 99-117 ◽  
Author(s):  
David Longo ◽  
Kent Koehn

Objective: The purpose of this review was to evaluate the evidence which supports the association between psychosocial factors and genital herpes simplex virus recurrences (HSV), as well as to examine the biological and psychological treatments for disease. Method: Forty-five studies were reviewed from the years 1928 to 1991. Studies were identified via computerized biographic literature search of Psychological Abstracts and Medline. Additional studies were located by inspection of key article reference sections. Studies were included in the review if the sample consisted of recurrent genital herpes sufferers and the design was either correlational or experimental. Cases studies were reviewed if they described HSV psychiatric treatment and provided outcome information. Results: Psychosocial variables are important elements in the prediction, maintenance, and management of recurrent genital herpes. Furthermore, the effectiveness of psychological treatment regimes may be explained via psychoimmunological theory. Conclusions: Psychosocial treatment should be considered as adjunctive therapy for biological treatment of recurrent HSV infections. Future research should address primary prevention of genital herpes and other sexually transmitted diseases, including HIV infections.


2009 ◽  
Vol 83 (20) ◽  
pp. 10664-10676 ◽  
Author(s):  
Amanda Kwant-Mitchell ◽  
Ali A. Ashkar ◽  
Kenneth L. Rosenthal

ABSTRACT Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is one of the most prevalent sexually transmitted diseases worldwide and a risk factor for acquiring human immunodeficiency virus. Although many vaccine candidates have shown promising results in animal models, they have failed to be effective in human trials. In this study, a humanized mouse strain was evaluated as a potential preclinical model for studying human immune responses to HSV-2 infection and vaccination. Immunodeficient mouse strains were examined for their abilities to develop human innate and adaptive immune cells after transplantation of human umbilical cord stem cells. A RAG2−/− γc−/− mouse strain with a BALB/c background was chosen as the most appropriate model and was then examined for its ability to mount innate and adaptive immune responses to intravaginal HSV-2 infection and immunization. After primary infection, human cells in the lymph nodes were able to generate a protective innate immune response and produce gamma interferon (IFN-γ). After intravaginal immunization and infection, human T cells and NK cells were found in the genital tract and iliac lymph nodes. In addition, human T cells in the spleen, lymph nodes, and vaginal tract were able to respond to stimulation with HSV-2 antigens by replicating and producing IFN-γ. Human B cells were also able to produce HSV-2-specific immunoglobulin G. These adaptive responses were also shown to be protective and reduce local viral replication in the genital tract. This approach provides a means for studying human immune responses in vivo using a small-animal model and may become an important preclinical tool.


Sign in / Sign up

Export Citation Format

Share Document