Thread by @Guillau13441190

@AaronSiriSG Good question, and right answers. Thanks @AaronSiriSG.
But don't worry ; the #mRNA #vaccine solution is in the "pipeline"...
sciencedirect.com/science/articl…

@AaronSiriSG "An RNA-Based Vaccine Platform for Use against Mycobacterium tuberculosis"
Larsen et al.
Published online 2023 Jan 5. doi: 10.3390/vaccines11010130
ncbi.nlm.nih.gov/pmc/articles/P…

@AaronSiriSG "Excitingly, in prime-boost strategies, the groups that received heterologous RNA-prime, protein-boost or combination immunizations demonstrated the greatest reduction in bacterial burden and a unique humoral and cellular immune response profile".

Excitingly...

@AaronSiriSG "Thankfully, renewed enthusiasm for TB vaccine research has been stimulated largely by two main pillars of preclinical and clinical advancements. First, the pursuit of correlates of protection (...) and second, the pursuit of cutting-edge vaccine delivery platforms"

Thankfully

@AaronSiriSG "Leveraging #RNA vaccines, for example, circumvents the challenges of protein manufacturing, reducing #vaccine development timelines from several years to months and reducing costs throughout #pipeline evaluations and deployment".

@AaronSiriSG "Indeed #BioNTech (Mainz, #Germany) has recently announced the initiation of a phase-one clinical trial for the safety testing of an #mRNA TB #vaccine candidate in collaboration with the Bill and Melinda #Gates Foundation ( Identifier: NCT05547464)."ClinicalTrials.gov

@AaronSiriSG Preclinical animal model.
"The mice were housed at the Infectious Disease Research Institute #biosafety level 3 animal facility under pathogen-free conditions and were handled in accordance with the specific guidelines of the #IDRI's Institutional Animal Care and Use Committee.

@AaronSiriSG "Reduced bacterial burden was calculated as the difference in the mean Log10 values between the groups(...)

7 mice/group is required to provide a statistical power of 95% with an alpha of 0.05 to detect a significant difference in the bacterial burden between the groups"

@AaronSiriSG "This repRNA platform has a number of advantages, including (1) a subgenomic promoter to amplify the expression of the antigen of interest, (2) exclusive cytoplasmic activity with no risks of nuclear genomic integration, and (3) sustained antigen production (...)"

@AaronSiriSG "Partnering repRNA with delivery formulations provides stability and protection from RNAses and removes the requirement for viral delivery, eliminating anti-vector immunity, which has been detrimental for promising candidates."

@AaronSiriSG "These data demonstrate that the repRNA platform is immunogenic and affords SOME [emphazised] prophylactic protection in a stringent preclinical mouse efficacy screening model of TB."

@AaronSiriSG "While intra-muscular vaccine strategies are not known for developing robust mucosal immune responses, we evaluated bronchoalveolar lavage fluid for anti-ID91 IgA responses at 3 weeks post-challenge. Not surprisingly, the magnitude of IgA produced by all regimens was low (...)"

@AaronSiriSG "while we observed modest protection from bacterial burden in the lungs of homologous protein and heterologous candidate vaccinated mice, there was an absence of protection observed in the spleen at this timepoint evaluated".

@AaronSiriSG 5. Conclusions

"The landscape of TB vaccines is ready for a dramatic surge forward.
(...)"

@AaronSiriSG Note : il s'agit ici d'une publication portant sur la tuberculose, pas sur la méningite évoquée dans le post de @AaronSiriSG ; l'objet est ici de présenter le "paysage" dessiné pour renouveler toute la panoplie vaccinale. Et le procédé.

@AaronSiriSG Au passage, concernant la méningite, #Pfizer nous propose désormais une nouvelle formule, le vaccin Pembraya.

Autorisé par la FDA fin octobre 2023
labeling.pfizer.com/ShowLabeling.a…
pfizer.com/news/press-rel…

@AaronSiriSG "Vaccination with PENBRAYA may not protect all who receive the vaccine against N. meningitidis group A, B, C, W, and Y infections"