Monkeypox virus A29L protein as the target for specific diagnosis and serological analysis.

Publisher: Springer International Country of Publication: Germany NLM ID: 8406612 Publication Model: Electronic Cited Medium: Internet ISSN: 1432-0614 (Electronic) Linking ISSN: 01757598 NLM ISO Abbreviation: Appl Microbiol Biotechnol Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer International, c1984-

Monkeypox virus*/immunology ; Monkeypox virus*/genetics ; Antibodies, Monoclonal*/immunology ; Antibodies, Viral*/blood ; Antibodies, Viral*/immunology ; Mpox (monkeypox)*/diagnosis; Humans ; Animals ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Serologic Tests/methods ; Viral Proteins/immunology ; Viral Proteins/genetics ; Mice ; Mice, Inbred BALB C ; Cross Reactions

The unexpected monkeypox (Mpox) outbreak has been reported in many non-endemic countries and regions since May 2022. The mutant strains of Mpox virus (MPXV) were found with higher infectivity and greater capability for sustained human-to-human transmission, posing a significant public health threat. MPXV A29L, a protein homolog of vaccinia virus (VACV) A27L, plays an important role in viral attachment to host cell membranes. Therefore, MPXV A29L is considered the diagnostic target and the potential vaccine candidate for eliciting neutralizing antibodies and protective immune responses. In response to the escalating Mpox outbreak, three monoclonal antibodies (mAbs) (2-9B, 3-8G, and 2-5H) targeting the different domains of MPXV A29L have been developed in the study. Among them, 2-5H is highly specific for MPXV A29L without exhibiting cross-reactivity with VACV A27L. The antibody pairing composed of 2-5H and 3-8G has been developed as the lateral flow immunochromatographic assay for specific detection of MPXV A29L. However, these three mAbs were unable to inhibit A29L binding to heparin column or prevent MPXV infection in the neutralization test assays. The results of the serological assays using the truncated A29L fragments as the antigens showed that the Mpox patient sera contained significantly lower levels of antibodies targeting the N-terminal 1-34 residues of A29L, suggesting that the N-terminal portion of A29L is less immunogenic upon natural infection. KEY POINTS: • MAbs 2-9B, 3-8G, and 2-5H neither interrupted A29L binding to heparin nor neutralized MPXV. • The LFIA composed of 3-8G and 2-5H can specifically distinguish MPXV A29L from VACV A27L. • Mpox patient sera contained lower levels of antibodies targeting the N-terminal portion of A29L.
Competing Interests: Declarations. Ethical approval: The animal experiment was approved by the IACUC of National Taiwan University (approval number: NTU-112-EL-00080) and implemented in accordance with the animal care and ethics guidelines. A written informed consent was obtained from all individual Mpox patients in the study, which was approved by the Institutional Review Board of National Taiwan University Hospital. Conflict of interest: The authors declare no competing interests.
(© 2024. The Author(s).)

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111-2320-B-002-047 National Science and Technology Council; 112-2740-B-002-004 National Science and Technology Council; 112-2321-B-002-013 National Science and Technology Council; 112L7255 National Taiwan University; 113L7226 National Taiwan University

Keywords: A29L protein; Lateral flow immunochromatographic assay; Monkeypox (Mpox); Monkeypox virus (MPXV); Monoclonal antibody; Serological assay

0 (Antibodies, Monoclonal)
0 (Antibodies, Viral)
0 (Antibodies, Neutralizing)
0 (Viral Proteins)

Date Created: 20241121 Date Completed: 20241121 Latest Revision: 20241124

20241126

PMC11582270

10.1007/s00253-024-13361-6

39570405