scholarly journals Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever

2007 ◽  
Vol 14 (10) ◽  
pp. 1285-1295 ◽  
Author(s):  
Dominique Fraillery ◽  
David Baud ◽  
Susana Yuk-Ying Pang ◽  
John Schiller ◽  
Martine Bobst ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Typhoid Fever ◽  
Salmonella Enterica ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Oral Immunization ◽  
Typhoid Vaccine ◽  
Serovar Typhimurium ◽  
Cervical Cancer Vaccine

ABSTRACT Human papillomavirus (HPV) vaccines based on L1 virus-like particles (VLPs) can prevent HPV-induced genital neoplasias, the precursors of cervical cancer. However, most cervical cancers occur in developing countries, where the implementation of expensive vaccines requiring multiple injections will be difficult. A live Salmonella-based vaccine could be a lower-cost alternative. We previously demonstrated that high HPV type 16 (HPV16)-neutralizing titers are induced after a single oral immunization of mice with attenuated Salmonella enterica serovar Typhimurium strains expressing a codon-optimized version of HPV16 L1 (L1S). To allow the testing of this type of vaccine in women, we constructed a new L1-expressing plasmid, kanL1S, and tested kanL1S recombinants of three Salmonella enterica serovar Typhi vaccine strains shown to be safe in humans, i.e., Ty21a, the actual licensed typhoid vaccine, and two highly immunogenic typhoid vaccine candidates, Ty800 and CVD908-htrA. In an intranasal mouse model of Salmonella serovar Typhi infection, Ty21a kanL1S was unique in inducing HPV16-neutralizing antibodies in serum and genital secretions, while anti-Salmonella responses were similar to those against the parental Ty21a vaccine. Electron microscopy examination of Ty21a kanL1S lysates showed that L1 assembled in capsomers and capsomer aggregates but not well-ordered VLPs. Comparison to the neutralizing antibody response induced by purified HPV16 L1 VLP immunizations in mice suggests that Ty21a kanL1S may be an effective prophylactic HPV vaccine. Ty21a has been widely used against typhoid fever in humans with a remarkable safety record. These finds encourage clinical testing of Ty21a kanL1S as a combined typhoid fever/cervical cancer vaccine with the potential for worldwide application.

scholarly journals Intravaginal Immunization of Mice with Recombinant Salmonella enterica Serovar Typhimurium Expressing Human Papillomavirus Type 16 Antigens as a Potential Route of Vaccination against Cervical Cancer

2008 ◽  
Vol 76 (5) ◽  
pp. 1940-1951 ◽  
Author(s):  
Hakim Echchannaoui ◽  
Matteo Bianchi ◽  
David Baud ◽  
Martine Bobst ◽  
Jean-Christophe Stehle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Tumor Cells ◽  
Salmonella Enterica ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Wide Range ◽  
Serovar Typhimurium

ABSTRACT Cervical cancer, the second leading cause of cancer deaths in women, is the consequence of high-risk human papillomavirus (HPV) infections. Toward the development of therapeutic vaccines that can induce both innate and adaptive mucosal immune responses, we analyzed intravaginal (ivag) vaccine delivery of live attenuated Salmonella enterica serovar Typhimurium expressing HPV16L1 as a model antigen. Innate immune responses were examined in cervicovaginal tissues by determining gene expression patterns by microarray analysis using nylon membranes imprinted with cDNA fragments coding for inflammation-associated genes. At 24 h, a wide range of genes, including those for chemokines and Th1- and Th2-type cytokine and chemokine receptors were up-regulated in mice ivag immunized with Salmonella compared to control mice. However, the majority of transcripts returned to their steady-state levels 1 week after immunization, suggesting a transient inflammatory response. Indeed, cervicovaginal histology of immunized mice showed a massive, but transient, infiltration of macrophages and neutrophils, while T cells were still increased after 7 days. Ivag immunization also induced humoral and antitumor immune responses, i.e., serum and vaginal anti-HPV16VLP antibody titers similar to those induced by oral immunization, and significant protection in tumor protection experiments using HPV16-expressing C3 tumor cells. These results show that ivag immunization with live attenuated Salmonella expressing HPV16 antigens modulates the local mucosal gene expression pattern into a transient proinflammatory profile, elicits strong systemic and mucosal immunity against HPV16, and confers protection against HPV16 tumor cells subcutaneously implanted in mice. Examination of the efficacy with which ivag HPV16E7E6 Salmonella induces regression of tumors located in cervicovaginal tissue is warranted.

scholarly journals Cervical cancer vaccine development

Sexual Health ◽  
2010 ◽  
Vol 7 (3) ◽  
pp. 230 ◽  
Author(s):  
Ian H. Frazer
Keyword(s):  
Cervical Cancer ◽  
Clinical Trials ◽  
Human Papillomavirus ◽  
Cancer Vaccine ◽  
Vaccine Development ◽  
Global Burden ◽  
Viral Capsids ◽  
Cervical Epithelium ◽  
Papillomavirus Vaccines ◽  
Cervical Cancer Vaccine

Cervical cancer is initiated by infection of cervical epithelium with human papillomavirus. Vaccines have been developed, incorporating papillomavirus viral capsids and alum based adjuvants. In extensive clinical trials these vaccines have been shown safe and effective in preventing infection with, and disease caused by, the papillomavirus genotypes they incorporate, in women not already infected. These vaccines have the potential to reduce the global burden of cervical cancer by up to 70%.

scholarly journals Immunoinformatics Study on Early 4 Protein of Human Papillomavirus Type 16 for Cervical Cancer Vaccine Peptide Candidate

2019 ◽  
Vol 4 (2) ◽  
pp. 252-262
Author(s):  
Yani Suryani ◽  
Opik Taupiqurrohman ◽  
Muhammad Yusuf ◽  
Toto Subroto ◽  
Sukma Nuswantara
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Amino Acid ◽  
Cancer Vaccine ◽  
Vaccine Candidate ◽  
Peptide Vaccine ◽  
Human Papillomavirus Type 16 ◽  
Cervical Cancer Vaccine ◽  
Peptide Candidate

 The aims of this study were to carry out testing of the early 4 protein of type 16 HPV through immunoinformatics meth-ods in an effort to get the peptide vaccine candidate for cervical cancer. The software used are IEDB-AR, CABSdock and Accelrys Discovery Study 4.5. Based on the analysis that sequence of ami-no acid lysine, leucine, leucine, glycine, serine, threonine, tryp-tophan, proline and threonine (KLLGSTWPT) and the sequence of amino acid tyrosine, tyrosine, valine, leucine, histidine, leucine, cysteine, leucine, alanine, alanine, threonine, lysine, tyrosine, pro-line and leucine (YYVLHLCLAATKYPL) are peptide vaccine can-didate for cervical cancer from the early 4 protein of HPV type 16 

scholarly journals Improved Efficiency of a Salmonella-Based Vaccine against Human Papillomavirus Type 16 Virus-Like Particles Achieved by Using a Codon-Optimized Version of L1

2004 ◽  
Vol 78 (23) ◽  
pp. 12901-12909 ◽  
Author(s):  
David Baud ◽  
Françoise Ponci ◽  
Martine Bobst ◽  
Pierre De Grandi ◽  
Denise Nardelli-Haefliger
Keyword(s):  
Neutralizing Antibodies ◽  
Hpv Infection ◽  
Oral Immunization ◽  
Human Papillomaviruses ◽  
Effective Vaccine ◽  
Virus Like Particle ◽  
Serovar Typhimurium ◽  
New Generation

ABSTRACT Cervical cancer results from cervical infection by human papillomaviruses (HPVs), especially HPV16. An effective vaccine against these HPVs is expected to have a dramatic impact on the incidence of this cancer and its precursor lesions. The leading candidate, a subunit prophylactic HPV virus-like particle (VLP) vaccine, can protect women from HPV infection. An alternative improved vaccine that avoids parenteral injection, that is efficient with a single dose, and that induces mucosal immunity might greatly facilitate vaccine implementation in different settings. In this study, we have constructed a new generation of recombinant Salmonella organisms that assemble HPV16 VLPs and induce high titers of neutralizing antibodies in mice after a single nasal or oral immunization with live bacteria. This was achieved through the expression of a HPV16 L1 capsid gene whose codon usage was optimized to fit with the most frequently used codons in Salmonella. Interestingly, the high immunogenicity of the new recombinant bacteria did not correlate with an increased expression of L1 VLPs but with a greater stability of the L1-expressing plasmid in vitro and in vivo in absence of antibiotic selection. Anti-HPV16 humoral and neutralizing responses were also observed with different Salmonella enterica serovar Typhimurium strains whose attenuating deletions have already been shown to be safe after oral vaccination of humans. Thus, our findings are a promising improvement toward a vaccine strain that could be tested in human volunteers.

scholarly journals Engineering and Preclinical Evaluation of Attenuated Nontyphoidal Salmonella Strains Serving as Live Oral Vaccines and as Reagent Strains

2011 ◽  
Vol 79 (10) ◽  
pp. 4175-4185 ◽  
Author(s):  
Sharon M. Tennant ◽  
Jin-Yuan Wang ◽  
James E. Galen ◽  
Raphael Simon ◽  
Marcela F. Pasetti ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Lethal Dose ◽  
Invasive Disease ◽  
Oral Immunization ◽  
Oral Vaccines ◽  
Wild Type ◽  
Lethal Challenge ◽  
Antibiotic Resistant ◽  
Content Type ◽  
Serovar Typhimurium

ABSTRACTWhile nontyphoidalSalmonella(NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuatedSalmonella entericaserovar Typhimurium andSalmonella entericaserovar Enteritidis strains that can serve as live oral vaccines and as “reagent strains” for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strainsS. TyphimuriumI77 andS. EnteritidisR11, respectively, were constructed by deletingguaBA, encoding guanine biosynthesis, andclpP, encoding a master protease regulator. TheclpPmutation resulted in a hyperflagellation phenotype. An additional deletion infliDyielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD50) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-typeS. TyphimuriumI77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection withS. EnteritidisR11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. SinceS. TyphimuriumandS. Enteritidisare the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.

Prophylactic human papillomavirus vaccines: the beginning of the end of cervical cancer

2004 ◽  
Vol 14 (5) ◽  
pp. 751-761 ◽  
Author(s):  
W. A. A. Tjalma ◽  
M. Arbyn ◽  
J. Paavonen ◽  
T. R. Van Waes ◽  
J. J. Bogers
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Neutralizing Antibodies ◽  
Hpv Vaccination ◽  
Phase Iii ◽  
Hpv Vaccines ◽  
Therapeutic Vaccines ◽  
The Status ◽  
Prophylactic Vaccines

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.

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