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Influence of Caudovirales Phages on Humoral Immunity in Mice.

ABSTRACT: Bacteriophages are promising antibacterial agents. Although they have been recognized as bacterial viruses and are considered to be non-interacting with eukaryotic cells, there is growing evidence that phages may have a significant impact on the immune system via interactions with macrophages, neutrophils, and T-cell polarization. In this study, the influence of phages of podovirus, siphovirus, and myovirus morphotypes on humoral immunity of CD-1 mice was investigated. In addition, tissue distribution of the phages was tested in these mice. No common patterns were found either in the distribution of phages in mice or in changes in the levels of cytokines in the sera of mice once injected with phages. Importantly, pre-existing IgM-class antibodies directed against capsid proteins of phages with myovirus and siphovirus morphotypes were identified in mice before immunization. After triple immunization of CD1-mice with phages without any adjuvant, levels of anti-phage serum polyclonal IgG antibodies increased. Immunogenic phage proteins recognized by IgM and/or IgG antibodies were identified using Western blot analysis and mass spectrometry. In addition, mice serum collected after immunization demonstrated neutralizing properties, leading to a substantial decrease in infectivity of investigated phages with myovirus and siphovirus morphotypes. Moreover, serum samples collected before administration of these phages exhibited some ability to reduce the phage infectivity. Furthermore, Proteus phage PM16 with podovirus morphotype did not elicit IgM or IgG antibodies in immunized mice, and no neutralizing activities against PM16 were revealed in mouse serum samples before and after immunization.

SUBMITTER: Chechushkov A

PROVIDER: S-EPMC8310086 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Hantaviruses are zoonotic pathogens found in parts of Europe, Asia, South America, and North America, which can cause renal and respiratory failure with fatality rates up to 40%. There are currently no FDA-approved vaccines or therapeutics for hantavirus-related diseases; however, it is evident that a robust neutralizing antibody response is critical for protection from severe disease. Although virologists first described this family of viruses in the 1950s, there is limited information on the neutralizing epitopes that exist on the hantavirus antigenic glycoproteins, Gn and Gc, and sites important for the design of effective therapeutics and vaccines. We provide a thorough summary of the hantavirus field from an immunological perspective. In particular, we discuss our current structural knowledge of antigenic proteins Gn and Gc, identification of B cell neutralizing epitopes, previously isolated monoclonal antibodies and their cross-reactivity between different hantavirus strains, and current developments toward vaccines and therapeutics. We conclude with some outstanding questions in the field and emphasize the need for additional studies of the human antibody response to hantavirus infection.IMPORTANCE Hantaviruses are pathogens that sometimes pass from animals to humans, and they are found in parts of Europe, Asia, and North and South America. When human infection occurs, these viruses can cause kidney or lung failure, and as many as 40% of infected people die. Currently, there are no vaccines or therapeutics for hantavirus-related diseases available. A first step in developing prevention measures is determining what type of immune response is protective. Increasingly it has become clear that the induction of a type of response called a neutralizing antibody response is critical for protection from severe disease. Although virologists first described this family of viruses in the 1950s, there is limited information on what features on the surface of hantaviruses are recognized by the immune system. Here, we review the current state of knowledge of this information, which is critical for the design of effective therapeutics and vaccines.

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Influence of Caudovirales Phages on Humoral Immunity in Mice.

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