NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE252919 Query DataSets for GSE252919
Status Public on Jan 10, 2024
Title FLUAV RAM-IGIP: A modified live influenza virus vaccine that enhances humoral and mucosal responses against influenza. Vaccine Encoding the IgA-Inducing Protein
Platform organism Influenza A virus
Sample organism Mus musculus
Experiment type Protein profiling by protein array
Summary Influenza A virus (FLUAV) poses a significant threat to both humans and animals. While vaccination serves as the primary defense against influenza, the effectiveness of currently approved vaccines is suboptimal. To address this issue, we have developed modified live virus (MLV) vaccines against influenza using genome rearrangement techniques targeting the internal gene segments of FLUAV. The rearranged M2 (RAM) strategy involves cloning the M2 ORF downstream of the PB1 ORF in segment 2 and incorporating multiple early stop codons within the M2 ORF in segment 7. Additionally, the IgA-inducing protein (IGIP) coding region was inserted into the HA segment to further attenuate the virus and enhance protective mucosal responses. RAM-IGIP viruses exhibit similar growth rates to wild type (WT) viruses in vitro and remain stable during multiple passages in cells and embryonated eggs. The safety, immunogenicity, and protective efficacy of the RAM-IGIP MLV vaccine against the prototypical 2009 pandemic H1N1 strain A/California/04/2009 (H1N1) (Ca/04) were evaluated in Balb/c mice and compared to a prototypic cold-adapted live attenuated virus vaccine. The results demonstrate that the RAM-IGIP virus exhibits attenuated virulence in vivo. Mice vaccinated with RAM-IGIP and subsequently challenged with an aggressive lethal dose of the Ca/04 strain exhibited complete protection. Analysis of the humoral immune response revealed that the inclusion of IGIP enhanced the production of neutralizing antibodies and augmented the antibody-dependent cellular cytotoxicity response. Similarly, the RAM-IGIP potentiated the mucosal immune response against various FLUAV subtypes. Moreover, increased antibodies against NP and NA responses were observed. These findings support the development of MLVs utilizing genome rearrangement strategies in conjunction with the incorporation of immunomodulators.
 
Overall design we have developed modified live virus (MLV) vaccines against influenza using genome rearrangement techniques targeting the internal gene segments of FLUAV. The rearranged M2 (RAM) strategy involves cloning the M2 ORF downstream of the PB1 ORF in segment 2 and incorporating multiple early stop codons within the M2 ORF in segment 7. Additionally, the IgA-inducing protein (IGIP) coding region was inserted into the HA segment to further attenuate the virus and enhance protective mucosal responses.
 
Contributor(s) Caceres CJ, Gay LC, Jain A, Mejias T, Cardenas M, Seibert B, Cargnin F, Cowan B, Geiger G, Vincent AL, Carnaccini S, Davies DH, Rajao D, Perez DR
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jan 10, 2024
Last update date Jan 10, 2024
Contact name Daniel Roberto Perez
E-mail(s) dperez1@uga.edu
Phone 7065425506
Organization name University of Georgia
Street address 953 College Station Road
City Athens
State/province GA
ZIP/Postal code 30602
Country USA
 
Platforms (1)
GPL30424 UGA#2 IBV array
Samples (112)
GSM8010263 SAMPLE 1 -Before challenge Female Mock Mouse 4
GSM8010264 SAMPLE 2 -Before challenge Female Mock Mouse 5
GSM8010265 SAMPLE 3 -Before challenge Male Mock Mouse 10
Relations
BioProject PRJNA1063248

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE252919_raw_data.txt.gz 45.2 Kb (ftp)(http) TXT
Processed data not provided for this record
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap