Hybrid multiepitope recombinant vaccine for protection against infection caused by group B streptococcus

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Abstract

BACKGROUND: Streptococcus agalactiae, commonly known as group B streptococcus, is an important pathogen responsible for severe and sometimes fatal invasive infections in newborns. It also poses a significant risk to older adults and those with weakened immune systems. Current preventive strategies primarily include the use of antibiotics to prevent maternal-to-fetal transmission of group B streptococcus and to treat established infections. The emergence of antibiotic-resistant strains has reduced the effectiveness of these treatments and highlighted the need for alternative preventive measures. Vaccines represent a promising complement to antibiotics, potentially providing broader and more effective protection against group B streptococcus infections.

AIM: The study aims to evaluate the immunogenic properties and protective efficacy of a newly developed chimeric recombinant protein vaccine (Su4) designed to combat group B streptococcus infections. This vaccine incorporates immunodominant epitopes from five group B streptococcus virulence factor proteins. The research investigated various vaccination methods in mice, followed by an analysis of the effectiveness of the induced immune response in providing protection against multiple forms of group B streptococcus infection.

MATERIALS AND METHODS: Female outbred mice (6–8 weeks of age) were immunized subcutaneously, intranasally, or intravaginally with a hybrid recombinant vaccine polypeptide Su4 at a dose of 20 μg with repeated administration at the same dose after 21 days. Blood samples were taken from the submandibular vein on days 20 and 40 after immunization. Immunogenicity was assessed by measuring the levels of specific IgG, IgG1, IgG2a and IgG3 using ELISA. The plates were coated with Su4 protein or recombinant peptide analogs of each of the five regions of the Su4 complex molecule, and antibody concentrations were determined using standard curves. Protective efficacy was assessed by the bacterial load in the lungs and vaginal lavages of mice infected with the group B streptococcus strain 6224 nasally or vaginally at a dose of 108 CFU/mouse. Bacterial concentrations in lung homogenates and vaginal washings were determined by plating the material on Columbia blood agar.

RESULTS: The study examined the protective effectiveness of vaccination with the polyepitope molecule Su4, consisting of linear determinants of five group B streptococcus proteins. Immunization by subcutaneous, intranasal and vaginal routes showed that the Su4 protein was immunogenic and caused the production of specific IgG. Subcutaneous immunization ensured the accumulation of the highest levels of antibodies. The immune response developed according to the Th2 type and predominantly led to the induction of IgG1 antibodies, potentially capable of opsonizing bacteria and initiating phagocytosis. Vaccination resulted in accelerated clearance of group B streptococcus from the vaginal cavity of mice following infection compared with the control group, demonstrating the protective effectiveness of the stimulated immune response in protecting against group B streptococcus infections.

CONCLUSIONS: The polyepitope chimeric recombinant protein Su4 is immunogenic via subcutaneous, intranasal, and vaginal administration, inducing a systemic IgG response specific to group B streptococcus proteins. This response enhances resistance to nasal and vaginal group B streptococcus infections, indicating that Su4 is a promising candidate for a multi-epitope vaccine against group B streptococcus.

About the authors

Galina F. Leontieva

Institute of Experimental Medicine

Email: galeonte@Yandex.ru
ORCID iD: 0000-0002-9876-6594
SPIN-code: 5204-9252

Cand. Sci. (Biology), Leading Research Associate of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Tatyana A. Kramskaya

Institute of Experimental Medicine

Author for correspondence.
Email: Tatyana.kramskaya@gmail.com
ORCID iD: 0000-0002-9408-6647
SPIN-code: 4529-3260

Cand. Sci. (Biology), Senior Research Associate of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Irina V. Koroleva

Institute of Experimental Medicine

Email: IVKoroleva@Yandex.ru
ORCID iD: 0000-0002-7966-5130
SPIN-code: 6456-7406

Cand. Sci. (Biology), Senior Research Associate of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Evgenia V. Kuleshevich

Institute of Experimental Medicine

Email: k-zh-v@mail.ru
SPIN-code: 6514-2213

Cand. Sci. (Biology), Research Associate of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Nadezhda V. Duplik

Institute of Experimental Medicine

Email: nadezhdaduplik@gmail.com
ORCID iD: 0000-0001-6595-7354
SPIN-code: 6628-3532

Cand. Sci. (Biology), Research Associate of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

Alexander N. Suvorov

Institute of Experimental Medicine

Email: alexander_suvorov1@hotmail.com
ORCID iD: 0000-0003-2312-5589
SPIN-code: 8062-5281

MD, Dr. Sci. (Medicine), Professor, Corresponding Member RAS, Head of Department of Molecular Microbiology

Russian Federation, 12 Academician Pavlov St., Saint Petersburg, 197022

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Supplementary files

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2. Fig. 1. Schematic representation and sequence alignment of fragments Bac, CspA, ScpB (C5a peptidase), ScaAB, and SspB1 within the hybrid protein molecules Su2 and Su4

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3. Fig. 2. IgG levels in blood serum: on day 20 following a single injection of Su4 protein ( а ); after repeated administration of Su4 protein ( b ). * Statistically significant differences, p < 0.05

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4. Fig. 3. Ratio of IgG1 to IgG2a subclass antibody levels following subcutaneous immunization of mice with the Su4 protein

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5. Fig. 4. Antibody levels against recombinant proteins incorporated into the chimeric protein Su4. * Statistically significant differences, p < 0.05

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6. Fig. 5. Quantification of group B streptococcus GBS in the lungs after intranasal challenge in groups of mice immunized via subcutaneous ( a ), intranasal ( b ), and intravaginal ( c ) routes. * Statistically significant differences, p < 0.05

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7. Fig. 6. Quantification of group B streptococcus in vaginal lavages at 3, 24, and 48 hours post-vaginal infection. * Statistically significant differences, p < 0.05

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