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Contribution of cryptic epitopes in designing a group A streptococcal vaccine.

ABSTRACT: A successful vaccine needs to target multiple strains of an organism. Streptococcus pyogenes is an organism that utilizes antigenic strain variation as a successful defence mechanism to circumvent the host immune response. Despite numerous efforts, there is currently no vaccine available for this organism. Here we review and discuss the significant obstacles to vaccine development, with a focus on how cryptic epitopes may provide a strategy to circumvent the obstacles of antigenic variation.

SUBMITTER: Ozberk V

PROVIDER: S-EPMC6150013 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Contribution of cryptic epitopes in designing a group A streptococcal vaccine.

Ozberk Victoria V Pandey Manisha M Good Michael F MF

Human vaccines & immunotherapeutics 20180614 8

A successful vaccine needs to target multiple strains of an organism. Streptococcus pyogenes is an organism that utilizes antigenic strain variation as a successful defence mechanism to circumvent the host immune response. Despite numerous efforts, there is currently no vaccine available for this organism. Here we review and discuss the significant obstacles to vaccine development, with a focus on how cryptic epitopes may provide a strategy to circumvent the obstacles of antigenic variation. ...[more]

PMID: 29873591

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Project description:Group B Streptococcus (GBS) is a leading cause of human neonatal bacterial disease, resulting in pneumonia, sepsis, meningitis and sometimes, death. Supportive preclinical studies of GBS capsular polysaccharide (CPS)-protein conjugate vaccines have led to several phase 1 and phase 2 trials in healthy, non-pregnant adults, which demonstrated that the vaccines, produced at the Channing Laboratory, were safe and immunogenic. However, evaluation of the safety and immunogenicity of a GBS conjugate vaccine administered to pregnant women demanded that it be manufactured under current good manufacturing practices (cGMP) and that it undergo developmental toxicity evaluation. In this report, we describe a GBS type III CPS-tetanus toxoid (III-TT) vaccine lot 3-1-96 manufactured and vialed under cGMP and our evaluation of the effect of this vaccine and of GBS type III CPS-specific antibody on conception and early- and late-stage fetal development in rabbits. III-TT lot 3-1-96 was compositionally similar to prototype III-TT lot 91-1, produced under non-GMP, and was potent in a mouse maternal vaccination-neonatal pup challenge model of GBS disease. Four groups of 30 female rabbits each were randomized to receive III-TT lot 3-1-96 vaccine, saline-alum, or combinations of these treatments before and after insemination. The dose of conjugated CPS on a weight basis was 1 microg/kg, mimicking the anticipated actual human dose. Based on the weight of the rabbits, this was 20- to 100-fold greater than the expected human dose. Does were pre-assigned to deliver litters naturally or have their kits delivered by Caesarean-section at gestation day 29, to assess late fetal development. Sera from does and kits were collected, and the presence of type III CPS-specific IgG was confirmed by quantitative ELISA. Based on all assessments, GBS type III-TT lot 3-1-96, nor antibody to it did not affect embryo fetal viability, sex ratio, growth or cause malformations (i.e., it was non-teratogenic). In addition, that III-TT lot 3-1-96 was found to be safe and immunogenic in two clinical studies involving healthy non-pregnant adults supports a clinical evaluation of this vaccine in pregnant women.

Dataset Information

Contribution of cryptic epitopes in designing a group A streptococcal vaccine.

Publications

Contribution of cryptic epitopes in designing a group A streptococcal vaccine.

Similar Datasets

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