Abstract: The present application relates to genetic engineering field, in particular to a CD4-Linker-DC-SIGN (CLD) protein mutant and application thereof. The CLD protein mutant is shown in SEQ ID NO. 4. The applicant mutates cysteine at position 60 of CD4 in the first generation CLD recombinant proteins into serine, and the obtained CLD protein mutant increases its ability to inhibit tested HIV-1 strains by 2-3 orders of magnitude. The neutralizing activity of the obtained CLD protein mutant against viruses is improved significantly, and such difference is more obvious in tested HIV-1T/F (transmitter/founder) viruses. The CLD protein mutant has greatly improved binding efficiency to HIV-1 virus. Furthermore, a complex formed by the CLD protein mutant or the recombinant CLD protein and an envelope protein can serve as an immunogen to highly induce antibodies targeting V1/V2 regions of the envelope protein, and shows wide application prospects.