TY - JOUR
T1 - Antigen self-anchoring onto bacteriophage T5 capsid-like particles for vaccine design
AU - Vernhes, Emeline
AU - Larbi Chérif, Linda
AU - Ducrot, Nicolas
AU - Vanbergue, Clément
AU - Ouldali, Malika
AU - Zig, Lena
AU - Sidibe, N’diaye
AU - Hoos, Sylviane
AU - Ramirez-Chamorro, Luis
AU - Renouard, Madalena
AU - Rossier, Ombeline
AU - England, Patrick
AU - Schoehn, Guy
AU - Boulanger, Pascale
AU - Benihoud, Karim
N1 - Publisher Copyright:
© 2024, The Author(s).
PY - 2024/12/1
Y1 - 2024/12/1
N2 - The promises of vaccines based on virus-like particles stimulate demand for universal non-infectious virus-like platforms that can be efficiently grafted with large antigens. Here, we harnessed the modularity and extreme affinity of the decoration protein pb10 for the capsid of bacteriophage T5. SPR experiments demonstrated that pb10 fused to mCherry or to the model antigen ovalbumin (Ova) retained picomolar affinity for DNA-free T5 capsid-like particles (T5-CLPs), while cryo-EM studies attested to the full occupancy of the 120 capsid binding sites. Mice immunization with CLP-bound pb10-Ova chimeras elicited strong long-lasting anti-Ova humoral responses involving a large panel of isotypes, as well as CD8+ T cell responses, without any extrinsic adjuvant. Therefore, T5-CLP constitutes a unique DNA-free bacteriophage capsid able to display a regular array of large antigens through highly efficient chemical-free anchoring. Its ability to elicit robust immune responses paves the way for further development of this novel vaccination platform.
AB - The promises of vaccines based on virus-like particles stimulate demand for universal non-infectious virus-like platforms that can be efficiently grafted with large antigens. Here, we harnessed the modularity and extreme affinity of the decoration protein pb10 for the capsid of bacteriophage T5. SPR experiments demonstrated that pb10 fused to mCherry or to the model antigen ovalbumin (Ova) retained picomolar affinity for DNA-free T5 capsid-like particles (T5-CLPs), while cryo-EM studies attested to the full occupancy of the 120 capsid binding sites. Mice immunization with CLP-bound pb10-Ova chimeras elicited strong long-lasting anti-Ova humoral responses involving a large panel of isotypes, as well as CD8+ T cell responses, without any extrinsic adjuvant. Therefore, T5-CLP constitutes a unique DNA-free bacteriophage capsid able to display a regular array of large antigens through highly efficient chemical-free anchoring. Its ability to elicit robust immune responses paves the way for further development of this novel vaccination platform.
UR - http://www.scopus.com/inward/record.url?scp=85181450568&partnerID=8YFLogxK
U2 - 10.1038/s41541-023-00798-5
DO - 10.1038/s41541-023-00798-5
M3 - Article
AN - SCOPUS:85181450568
SN - 2059-0105
VL - 9
JO - npj Vaccines
JF - npj Vaccines
IS - 1
M1 - 6
ER -