Protective immunity induced by an intranasal multivalent vaccine comprising 10 Lactococcus lactis strains expressing highly prevalent M-protein antigens derived from Group A Streptococcus

Aniela Wozniak, Natalia Scioscia, Patricia C. García, James Dale, Braulio A. Paillavil, Paulette Legarraga, Francisco J. Salazar-Echegarai, Susan M. Bueno, Alexis M. Kalergis

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Streptococcus pyogenes (group A Streptococcus) causes diseases ranging from mild pharyngitis to severe invasive infections. The N-terminal fragment of streptococcal M protein elicits protective antibodies and is an attractive vaccine target. However, this N- terminal fragment is hypervariable: there are more than 200 different M types. In this study, an intranasal live bacterial vaccine comprising 10 strains of Lactococcus lactis, each expressing one N-terminal fragment of M protein, has been developed. Live bacterial-vectored vaccines cost less to manufacture because the processes involved are less complex than those required for production of protein subunit vaccines. Moreover, intranasal administration does not require syringes or specialized personnel. Evaluation of individual vaccine types (M1, M2, M3, M4, M6, M9, M12, M22, M28 and M77) showed that most of them protected mice against challenge with virulent S. pyogenes. All 10 strains combined in a 10-valent vaccine (M×10) induced serum and bronchoalveolar lavage IgG titers that ranged from three- to 10-fold those of unimmunized mice. After intranasal challenge with M28 streptococci, survival of M×10-immunized mice was significantly higher than that of unimmunized mice. In contrast, when mice were challenged with M75 streptococci, survival of M×10-immunized mice did not differ significantly from that of unimmunized mice. Mx-10 immunized mice had significantly less S. pyogenes in oropharyngeal washes and developed less severe disease symptoms after challenge than did unimmunized mice. Our L. lactis-based vaccine may provide an alternative solution to development of broadly protective group A streptococcal vaccines.

Original languageEnglish (US)
Pages (from-to)395-404
Number of pages10
JournalMicrobiology and immunology
Volume62
Issue number6
DOIs
StatePublished - Jun 1 2018

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Lactococcus lactis
Streptococcus
Immunity
Vaccines
Antigens
Proteins
Streptococcus pyogenes
Bacterial Vaccines
Streptococcal Vaccines
Intranasal Administration
Subunit Vaccines
Pharyngitis
Syringes
Protein Subunits
Bronchoalveolar Lavage
Immunoglobulin G
Costs and Cost Analysis
Antibodies

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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Protective immunity induced by an intranasal multivalent vaccine comprising 10 Lactococcus lactis strains expressing highly prevalent M-protein antigens derived from Group A Streptococcus. / Wozniak, Aniela; Scioscia, Natalia; García, Patricia C.; Dale, James; Paillavil, Braulio A.; Legarraga, Paulette; Salazar-Echegarai, Francisco J.; Bueno, Susan M.; Kalergis, Alexis M.

In: Microbiology and immunology, Vol. 62, No. 6, 01.06.2018, p. 395-404.

Research output: Contribution to journalArticle

Wozniak, Aniela ; Scioscia, Natalia ; García, Patricia C. ; Dale, James ; Paillavil, Braulio A. ; Legarraga, Paulette ; Salazar-Echegarai, Francisco J. ; Bueno, Susan M. ; Kalergis, Alexis M. / Protective immunity induced by an intranasal multivalent vaccine comprising 10 Lactococcus lactis strains expressing highly prevalent M-protein antigens derived from Group A Streptococcus. In: Microbiology and immunology. 2018 ; Vol. 62, No. 6. pp. 395-404.
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AU - Dale, James

AU - Paillavil, Braulio A.

AU - Legarraga, Paulette

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AU - Bueno, Susan M.

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