Dataset Information

Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice.

ABSTRACT: Influenza and its bacterial complications are a leading cause of morbidity and mortality worldwide. The effect of combined immunization with live influenza vaccine and recombinant chimeric pneumococcal protein in dual infection caused by influenza H1N1 and S. pneumoniae (serotype 3) has been studied. The combined vaccine consisted of the strain A/California/2009/38 (H1N1) pdm and chimeric recombinant protein PSPF composed of immunodominant fragments of the surface virulence factors of S. pneumoniae-PsaA, PspA, and Shr1875-associated with modified salmonella flagellin. Vaccinated mice were infected with the influenza virus 24 hours before or 24 hours after the onset of pneumococcal infection. The protective effect of combined vaccination was shown on both models of viral-bacterial infection.

SUBMITTER: Kramskaya T

PROVIDER: S-EPMC6742370 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice.

Kramskaya T T Leontieva G G Desheva Yu Y Grabovskaya K K Gupalova T T Rudenko L L Suvorov A A

PloS one 20190912 9

Influenza and its bacterial complications are a leading cause of morbidity and mortality worldwide. The effect of combined immunization with live influenza vaccine and recombinant chimeric pneumococcal protein in dual infection caused by influenza H1N1 and S. pneumoniae (serotype 3) has been studied. The combined vaccine consisted of the strain A/California/2009/38 (H1N1) pdm and chimeric recombinant protein PSPF composed of immunodominant fragments of the surface virulence factors of S. pneumon ...[more]

PMID: 31513620

Similar Datasets

Project description:Recurring epizootic influenza A virus (IAV) infections in domestic livestock such as swine and poultry are associated with a substantial economic burden and pose a constant threat to human health. Therefore, universally applicable and safe animal vaccines are urgently needed. We recently demonstrated that a reassortment-incompatible chimeric bat H17N10 virus harboring the A/swan/Germany/R65/2006 (H5N1) surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) can be efficiently used as a modified live influenza vaccine (MLIV). To ensure vaccine safety and, thus, improve the applicability of this novel MLIV for mammalian usage, we performed consecutive passaging in eggs and chickens. Following passaging, we identified mutations in the viral polymerase subunits PB2 (I382S), PB1 (Q694H and I695K), and PA (E141K). Strikingly, recombinant chimeric viruses encoding these mutations showed no growth deficiencies in avian cells but displayed impaired growth in human cells and mice. Homologous prime-boost immunization of mice with one of these avian-adapted chimeric viruses, designated rR65mono/H17N10EP18, elicited a strong neutralizing antibody response and conferred full protection against lethal highly pathogenic avian influenza virus (HPAIV) H5N1 challenge infection. Importantly, the insertion of the avian-adaptive mutations into the conventional avian-like A/SC35M/1980 (H7N7) and prototypic human A/PR/8/34 (H1N1) viruses led to attenuated viral growth in human cells and mice. Collectively, our data show that the polymerase mutations identified here can be utilized to further improve the safety of our novel H17N10-based MLIV candidates for future mammalian applications. IMPORTANCE Recurring influenza A virus outbreaks in livestock, particularly in swine and chickens, pose a constant threat to humans. Live attenuated influenza vaccines (LAIVs) might be a potent tool to prevent epizootic outbreaks and the resulting human IAV infections; however, LAIVs have several disadvantages, especially in terms of reassortment with circulating IAVs. Notably, the newly identified bat influenza A viruses H17N10 and H18N11 cannot reassort with conventional IAVs. Chimeric bat influenza A viruses encoding surface glycoproteins of conventional IAV subtypes might thus function as safe and applicable modified live influenza vaccines (MLIVs).

Project description:Attenuated Salmonella enterica serovar Typhimurium expressing recombinant antigens from other pathogens elicits primarily a Th1-type dominant immune response to both recombinant and Salmonella antigens. The immunogenicity and appropriate subcellular location of the recombinant antigen in the Salmonella vaccine strain may contribute to augmenting immune responses by facilitating adequate exposure of recombinant antigen to antigen-presenting cells for processing. To allow for secretion from gram-negative bacteria and overexpression of antigen, a DNA fragment encoding a highly antigenic alpha-helical region of PspA (pneumococcal surface protein A) was subcloned downstream from the beta-lactamase signal sequence in the multicopy Asd(+) pYA3493 vector to create pYA3494. pYA3493 was derived from a class of Asd(+) vectors with reduced expression of Asd to minimize selective disadvantage and enhance immunization of expressed recombinant antigens. The S. enterica serovar Typhimurium vaccine strain was constructed by the introduction of deletion mutations Delta crp-28 and Delta asdA16. Approximately 50% of the recombinant PspA (rPspA) expressed in a Salmonella strain harboring pYA3494 was detected in the combined supernatant and periplasmic fractions of broth-grown recombinant Salmonella. After a single oral immunization in BALB/c mice with 10(9) CFU of the recombinant Salmonella vaccine strain carrying pYA3494, immunoglobulin G (IgG) antibody responses were stimulated to both the heterologous antigen rPspA and Salmonella lipopolysaccharide (LPS) and outer membrane proteins (OMPs). About half, and even more at later times after immunization, of the antibodies induced to rPspA were IgG1 (indicating a Th2-type response), whereas 60 to 70% of the antibodies to LPS and 80 to 90% of those to OMPs were IgG2a (indicating a Th1-type response). A sublethal infection with Streptococcus pneumoniae WU2 boosted PspA antibody levels and maintained IgG2a/IgG1 ratios similar to those seen before the challenge. Oral immunization with Salmonella-PspA vaccine protected 60% of immunized mice from death after intraperitoneal challenge with 50 times the 50% lethal dose of virulent S. pneumoniae WU2.

Dataset Information

Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice.

Publications

Combined immunization with attenuated live influenza vaccine and chimeric pneumococcal recombinant protein improves the outcome of virus-bacterial infection in mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets