The A29L protein is a 110-amino-acid surface protein expressed on the intracellular mature virion (IMV) of MPXV. It facilitates viral entry by binding heparan sulfate on host cells and serves as a major antigenic target for neutralizing antibodies . Homologous to the vaccinia virus A27L protein, A29L is evolutionarily conserved across orthopoxviruses .
Heparan-binding domain (HBD): Mediates viral attachment to host cells .
Epitope regions: Linear epitopes (e.g., 21–49 aa) near the HBD are critical for neutralization .
A29L antibodies block viral adhesion by targeting epitopes adjacent to the HBD, disrupting interactions with glycosaminoglycans (GAGs) .
Combining 9F8, 3A1, and 2D1 antibodies enhances neutralization against vaccinia virus (VACV) by >90% .
| Assay Type | Sensitivity | Specificity | Time-to-Result | Source |
|---|---|---|---|---|
| SiTQD-ICA | 5 pg/mL | 100% (vs. chickenpox/respiratory pathogens) | 20 minutes | |
| LFIA (2-5H/3-8G) | 1 ng/mL | MPXV-specific | 15 minutes |
BALB/c mice immunized with A29L mRNA-LNP produced high-affinity antibodies (EC₅₀ < 10 nM) within 24 days .