Clinical and microbiological response of mice to intranasal inoculation with Lactococcus lactis expressing Group A Streptococcus antigens, to be used as an anti-streptococcal vaccine

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

Research output: Contribution to journalArticle

Abstract

Protein subunit vaccines are often preferred because of their protective efficacy and safety. Lactic acid bacteria expressing heterologous antigens constitute a promising approach to vaccine development. However, their safety in terms of toxicity and bacterial clearance must be evaluated. Anti-Streptococcus pyogenes (S. pyogenes) vaccines face additional safety concerns because they may elicit autoimmune responses. The assessment of toxicity, clearance and autoimmunity of an anti-streptococcal vaccine based on Lactococcus lactis (L. lactis) expressing 10 different M protein fragments from S. pyogenes (L. lactis-Mx10) is here reported. Clearance of L. lactis from the oropharynges of immunocompetent mice and mice devoid of T/B lymphocytes mice was achieved without using antibiotics. The absence of autoimmune responses against human tissues was demonstrated with human brain, heart and kidney. Assessment of toxicity showed that leucocyte counts and selected serum biochemical factors were not affected in L. lactis-Mx10-immunized mice. In contrast, mice immunized with L. lactis wild type vector (L. lactis-WT) showed increased neutrophil and monocyte counts and altered histopathology of lymph nodes, lungs and nasal epithelium. Two days after immunization, L. lactis-Mx10-immunized and L. lactis-WT-immunized mice weighed significantly less than unimmunized mice. However, both groups of immunized mice recovered their body weights by Day 6. Our results demonstrate that L. lactis-WT, but not the vaccine L. lactis-Mx10, induces alterations in certain hematologic and histopathological variables. We consider these data a major contribution to data on L. lactis as a bacterial vector for vaccine delivery.

Original languageEnglish (US)
Pages (from-to)711-719
Number of pages9
JournalMicrobiology and Immunology
Volume62
Issue number11
DOIs
StatePublished - Nov 1 2018

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Streptococcal Vaccines
Lactococcus lactis
Streptococcus
Antigens
Autoimmunity
Vaccines
Streptococcus pyogenes
Safety
Bacterial Vaccines
Heterophile Antigens
Subunit Vaccines
Oropharynx
Nasal Mucosa
Protein Subunits
Leukocyte Count
Monocytes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Virology

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Clinical and microbiological response of mice to intranasal inoculation with Lactococcus lactis expressing Group A Streptococcus antigens, to be used as an anti-streptococcal vaccine. / García, Patricia C.; Paillavil, Braulio A.; Scioscia, Natalia; Dale, James; Legarraga, Paulette; Salazar-Echegarai, Francisco J.; Bueno, Susan M.; Kalergis, Alexis M.; Wozniak, Aniela.

In: Microbiology and Immunology, Vol. 62, No. 11, 01.11.2018, p. 711-719.

Research output: Contribution to journalArticle

García, Patricia C. ; Paillavil, Braulio A. ; Scioscia, Natalia ; Dale, James ; Legarraga, Paulette ; Salazar-Echegarai, Francisco J. ; Bueno, Susan M. ; Kalergis, Alexis M. ; Wozniak, Aniela. / Clinical and microbiological response of mice to intranasal inoculation with Lactococcus lactis expressing Group A Streptococcus antigens, to be used as an anti-streptococcal vaccine. In: Microbiology and Immunology. 2018 ; Vol. 62, No. 11. pp. 711-719.
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AU - Scioscia, Natalia

AU - Dale, James

AU - Legarraga, Paulette

AU - Salazar-Echegarai, Francisco J.

AU - Bueno, Susan M.

AU - Kalergis, Alexis M.

AU - Wozniak, Aniela

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AB - Protein subunit vaccines are often preferred because of their protective efficacy and safety. Lactic acid bacteria expressing heterologous antigens constitute a promising approach to vaccine development. However, their safety in terms of toxicity and bacterial clearance must be evaluated. Anti-Streptococcus pyogenes (S. pyogenes) vaccines face additional safety concerns because they may elicit autoimmune responses. The assessment of toxicity, clearance and autoimmunity of an anti-streptococcal vaccine based on Lactococcus lactis (L. lactis) expressing 10 different M protein fragments from S. pyogenes (L. lactis-Mx10) is here reported. Clearance of L. lactis from the oropharynges of immunocompetent mice and mice devoid of T/B lymphocytes mice was achieved without using antibiotics. The absence of autoimmune responses against human tissues was demonstrated with human brain, heart and kidney. Assessment of toxicity showed that leucocyte counts and selected serum biochemical factors were not affected in L. lactis-Mx10-immunized mice. In contrast, mice immunized with L. lactis wild type vector (L. lactis-WT) showed increased neutrophil and monocyte counts and altered histopathology of lymph nodes, lungs and nasal epithelium. Two days after immunization, L. lactis-Mx10-immunized and L. lactis-WT-immunized mice weighed significantly less than unimmunized mice. However, both groups of immunized mice recovered their body weights by Day 6. Our results demonstrate that L. lactis-WT, but not the vaccine L. lactis-Mx10, induces alterations in certain hematologic and histopathological variables. We consider these data a major contribution to data on L. lactis as a bacterial vector for vaccine delivery.

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