Evaluation of the intramuscular administration of Cervarix™ vaccine on fertility, pre- and post-natal development in rats

Segal, Lawrence; Wilby, Owen K.; Willoughby, Chris R.; Veenstra, Stéphane; Deschamps, Marguerite

doi:10.1016/j.reprotox.2010.09.001

Cited by 30 publications

(14 citation statements)

References 29 publications

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“…The housing conditions were previously described [42]. Briefly, the rats were allowed free access to a standard rodent diet with no added antibiotic or other chemotherapeutic or prophylactic agent.…”

Section: Treatment and Administrationmentioning

confidence: 99%

“…Four-day-old offspring selected for blood sampling were sacrificed by decapitation. Macroscopic pathology examinations of the females, fetuses, and offspring were performed as previously described [42].…”

Section: Cesarean Section Uterine/ovary Evaluations and Fetal Examinmentioning

confidence: 99%

“…Parturition and post-natal observations, and the duration of gestation were evaluated as previously described [42]. From day 20 after mating, females were inspected three times daily for evidence of parturition.…”

Section: Parturition and Post-natal Observations (Study 1)mentioning

confidence: 99%

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Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

Destexhe

Stannard²,

Wilby³

et al. 2015

Reproductive Toxicology

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We assessed potential toxic effects of the MAGE-A3 Cancer Immunotherapeutic on female fertility and embryo-fetal, pre- and post-natal development in rats and on male fertility in rats and monkeys. Three groups of 48 female (Study 1) or 22 male (Study 2) CD rats received 5 or 3 injections of 100μL of saline, AS15 immunostimulant, or MAGE-A3 Cancer Immunotherapeutic (MAGE-A3 recombinant protein combined with AS15) at various timepoints pre- or post-mating. Male Cynomolgus monkeys (Study 3) received 8 injections of 500μL of saline (n=2) or the MAGE-A3 Cancer Immunotherapeutic (n=6) every 2 weeks. Rats were sacrificed on gestation day 20 or lactation day 25 (Study 1) or 9 weeks after first injection (Study 2) and monkeys, 3 days or 8 weeks after last injection. Injections were well tolerated. Female rat mating performance or fertility, pre- and post-natal survival, offspring development up to 25 days of age, and male mating performance (rats) or fertility parameters (rats and monkeys) were unaffected.

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Section: Treatment and Administrationmentioning

confidence: 99%

Section: Cesarean Section Uterine/ovary Evaluations and Fetal Examinmentioning

confidence: 99%

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Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

Destexhe

Stannard²,

Wilby³

et al. 2015

Reproductive Toxicology

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“…Currently, the cervical cancer prophylactic vaccines based on human papillomavirus (HPV) L1 virus-like particles (VLPs), including Gardasil (HPV6/11/16/18 quatrivalent vaccine developed by Merck, Kenilworth, NJ, USA) and Cervarix (HPV16/18 bivalent vaccine developed by GlaxoSmithKline, Brentford, UK) have been approved in a number of developed countries, and can induce satisfactory protective effects (5,6). However, this protection is type-specific and there is weak or no protection against other HPV types.…”

Section: Introductionmentioning

confidence: 99%

Protein transduction domain can enhance the humoral immunity and cross-protection of HPV16L2 peptide vaccines

Guo

et al. 2016

Biomedical Reports

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Abstract. Due to type-specificity, commercially available human papillomavirus (HPV) vaccines are only effective against homologous HPV serotypes, providing limited protection. Recent studies have highlighted the role of HPV minor capsid protein (known as L2) in inducing cross-protection. The N-terminal peptides of L2 contain conserved cross-response epitopes that can induce neutralizing antibodies against heterogeneous HPVs. However, when compared with L1, these peptides have lower immunogenicity, which limits the application of these vaccines. The protein transduction domain (PTD), located in the Tat protein of human immunodeficiency virus, facilitates delivery of DNA, peptides, proteins and virus particles into cells by unknown mechanisms, and has been reported to enhance immunogenicity of several antigens. In the present study, two peptides derived from the N-terminal of HPV16L2 were chosen as model antigens and constructed a series of L2 peptide vaccines by either fusing or mixing with PTD. Subsequently their immunogenicity was evaluated. The results indicated that the L2 peptides fused with PTD show considerably enhanced humoral immunity. In particular, they increased the titer of cross-neutralizing antibodies, while L2 peptides that had only been mixed with PTD induced only small cross-protection responses. Overall, the data suggest that fusion of L2 peptides with PTD significantly enhances their cross-protection and may be a promising strategy for the development of broad-spectrum HPV prophylactic vaccines. IntroductionTat-protein transduction domain (PTD) [the PTD domain of human immunodeficiency virus (HIV)-tat] is a peptide of 9-11 amino acids in length and is predominantly comprised of basic amino acids, such as arginine and/or lysine (1-3). Accumulating evidence indicates that PTD has the capability to carry proteins, peptides, nucleic acid and viral particles into cells. Although the detailed mechanisms for transduction remain to be elucidated, negatively charged heparan sulphate on the cell surface could have an important role in this process. Due to its unique characteristics, PTD has numerous applications, including delivery of functional proteins, viral particles and enhancing the DNA (RNA) transfection efficiency. A previous study has also suggested that PTD combined with certain antigens can enhance immunogenicity (4).Currently, the cervical cancer prophylactic vaccines based on human papillomavirus (HPV) L1 virus-like particles (VLPs), including Gardasil (HPV6/11/16/18 quatrivalent vaccine developed by Merck, Kenilworth, NJ, USA) and Cervarix (HPV16/18 bivalent vaccine developed by GlaxoSmithKline, Brentford, UK) have been approved in a number of developed countries, and can induce satisfactory protective effects (5,6). However, this protection is type-specific and there is weak or no protection against other HPV types. The discovery of cross-neutralizing responses induced by L2 derived from rabbit, bovine and human papillomavirus underline the potential application as a promising broad-spec...

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“…[5354] However, since adequate and well-controlled studies in pregnant women are lacking (pregnancy category B), vaccine should not be given to women known to be pregnant. Women who accidentally receive the vaccine while pregnant should delay further shots till pregnancy is over.…”

Section: Introductionmentioning

confidence: 99%

Human papilloma virus vaccines: Current scenario

Pandhi

Sonthalia

2011

Indian J Sex Transm Dis

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Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9–13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40–60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil® is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9–26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9–26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10–25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines.

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Evaluation of the intramuscular administration of Cervarix™ vaccine on fertility, pre- and post-natal development in rats

Cited by 30 publications

References 29 publications

Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

Nonclinical reproductive and developmental safety evaluation of the MAGE-A3 Cancer Immunotherapeutic, a therapeutic vaccine for cancer treatment

Protein transduction domain can enhance the humoral immunity and cross-protection of HPV16L2 peptide vaccines

Human papilloma virus vaccines: Current scenario

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