Rotavirus VP6 protein mucosally delivered by cell wall-derived particles from Lactococcus lactis induces protection against infection in a murine model

• Published in: PloS one Vol. 13; no. 9; p. e0203700
• Main Authors: Temprana, C Facundo, Argüelles, Marcelo H, Gutierrez, Nicolás M, Barril, Patricia A, Esteban, Laura E, Silvestre, Dalila, Mandile, Marcelo G, Glikmann, Graciela, Castello, Alejandro A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07-09-2018; Public Library of Science (PLoS)
• Subjects: Analysis; Animal models; Animals; Antibodies; Antibody Specificity; Antigens; Antigens, Viral - immunology; Antigens, Viral - metabolism; Biology and Life Sciences; Capsid Proteins - immunology; Capsid Proteins - metabolism; Care and treatment; Cell Wall - metabolism; Cell walls; Children; Disease Models, Animal; Drug Carriers - metabolism; E coli; Flow cytometry; Gastroenteritis; Gel electrophoresis; Health aspects; Immune response; Immune system; Immunization; Immunogenicity; Immunoglobulin A; Immunoglobulin A - immunology; Immunoglobulin G; Immunoglobulin G - immunology; Immunoglobulins; Infections; Lactococcus lactis; Lactococcus lactis - cytology; Licenses; Male; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mortality; Mucosa; Mucous Membrane - metabolism; Particulates; Patient outcomes; Proteins; Research and Analysis Methods; Risk factors; Rotavirus; Rotavirus - physiology; Rotavirus Infections - prevention & control; Rotaviruses; Socioeconomics; Sodium lauryl sulfate; Vaccines; Virology; Viruses; VP6 protein; Argentina
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203700

Rotaviruses are the primary cause of acute gastroenteritis in children worldwide. Although the implementation of live attenuated vaccines has reduced the number of rotavirus-associated deaths, variance in their effectiveness has been reported in different countries. This fact, among other concerns, leads to continuous efforts for the development of new generation of vaccines against rotavirus.In this work, we describe the obtention of cell wall-derived particles from a recombinant Lactococcus lactis expressing a cell wall-anchored version of the rotavirus VP6 protein. After confirming by SDS-PAGE, Western blot, flow cytometry and electronic immunomicroscopy that these particles were carrying the VP6 protein, their immunogenic potential was evaluated in adult BALB/c mice. For that, mucosal immunizations (oral or intranasal), with or without the dmLT [(double mutant Escherichia coli heat labile toxin LT(R192G/L211A)] adjuvant were performed. The results showed that these cell wall-derived particles were able to generate anti-rotavirus IgG and IgA antibodies only when administered intranasally, whether the adjuvant was present or not. However, the presence of dmLT was necessary to confer protection against rotavirus infection, which was evidenced by a 79.5 percent viral shedding reduction.In summary, this work describes the production of cell wall-derived particles which were able to induce a protective immune response after intranasal immunization. Further studies are needed to characterize the immune response elicited by these particles as well as to determine their potential as an alternative to the use of live L. lactis for mucosal antigen delivery.