tetano
Editor, Senior Moderator
Hum Vaccin Immunother. 2017 Nov 14:0. doi: 10.1080/21645515.2017.1403703. [Epub ahead of print]
[h=1]Generation and testing anti-influenza human monoclonal antibodies in a new humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD).[/h] Mendoza M[SUP]1[/SUP], Ballesteros A[SUP]2[/SUP], Qi Q[SUP]1[/SUP], Sang LP[SUP]1[/SUP], Shashikumar S[SUP]3[/SUP], Casares S[SUP]1,[/SUP][SUP]3[/SUP], Brumeanu TD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rγc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb). DRAGA mouse was also found to be suitable for influenza virus infection, as it can clear a sub-lethal infection and sustain a lethal infection with PR8/A/34 influenza virus. The hu-mAbs were designed for targeting a human B-cell epitope ([SUP]180[/SUP]WGIHHPPNSKEQ QNLY[SUP]195[/SUP]) of hemagglutinin (HA) envelope protein of PR8/A/34 (H1N1) virus with high homology among seven influenza type A viruses. A single administration of HA[SUB]180-195[/SUB] specific hu-mAb in PR8-infected DRAGA mice significantly delayed the lethality by reducing the lung damage. The results demonstrated that DRAGA mouse is a suitable tool to (i) generate heterotype cross-reactive, anti-influenza human monoclonal antibodies, (ii) serve as a humanized mouse model for influenza infection, and (iii) assess the efficacy of anti-influenza antibody-based therapeutics for human use.
[h=4]KEYWORDS:[/h] Anti-flu antibody therapy; Human influenza infection model; Human monoclonal antibodies; Humanized mice
PMID: 29135340 DOI: 10.1080/21645515.2017.1403703
[h=1]Generation and testing anti-influenza human monoclonal antibodies in a new humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO. IL-2Rγc KO. NOD).[/h] Mendoza M[SUP]1[/SUP], Ballesteros A[SUP]2[/SUP], Qi Q[SUP]1[/SUP], Sang LP[SUP]1[/SUP], Shashikumar S[SUP]3[/SUP], Casares S[SUP]1,[/SUP][SUP]3[/SUP], Brumeanu TD[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Pandemic outbreaks of influenza type A viruses have resulted in numerous fatalities around the globe. Since the conventional influenza vaccines (CIV) provide less than 20% protection for individuals with weak immune system, it has been considered that broadly cross-neutralizing antibodies may provide a better protection. Herein, we showed that a recently generated humanized mouse (DRAGA mouse; HLA-A2. HLA-DR4. Rag1KO. IL-2Rγc KO. NOD) that lacks the murine immune system and expresses a functional human immune system can be used to generate cross-reactive, human anti-influenza monoclonal antibodies (hu-mAb). DRAGA mouse was also found to be suitable for influenza virus infection, as it can clear a sub-lethal infection and sustain a lethal infection with PR8/A/34 influenza virus. The hu-mAbs were designed for targeting a human B-cell epitope ([SUP]180[/SUP]WGIHHPPNSKEQ QNLY[SUP]195[/SUP]) of hemagglutinin (HA) envelope protein of PR8/A/34 (H1N1) virus with high homology among seven influenza type A viruses. A single administration of HA[SUB]180-195[/SUB] specific hu-mAb in PR8-infected DRAGA mice significantly delayed the lethality by reducing the lung damage. The results demonstrated that DRAGA mouse is a suitable tool to (i) generate heterotype cross-reactive, anti-influenza human monoclonal antibodies, (ii) serve as a humanized mouse model for influenza infection, and (iii) assess the efficacy of anti-influenza antibody-based therapeutics for human use.
[h=4]KEYWORDS:[/h] Anti-flu antibody therapy; Human influenza infection model; Human monoclonal antibodies; Humanized mice
PMID: 29135340 DOI: 10.1080/21645515.2017.1403703