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Hyper-Enriched Anti-RSV Immunoglobulins Nasally Administered: A Promising Approach for Respiratory Syncytial Virus Prophylaxis.
Jacque, Emilie; Chottin, Claire; Laubreton, Daphné; Nogre, Michel; Ferret, Cécile; de Marcos, Sandrine; Baptista, Linda; Drajac, Carole; Mondon, Philippe; De Romeuf, Christophe; Rameix-Welti, Marie-Anne; Eléouët, Jean-François; Chtourou, Sami; Riffault, Sabine; Perret, Gérald; Descamps, Delphyne.
  • Jacque E; LFB Biotechnologies, Les Ulis, France.
  • Chottin C; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • Laubreton D; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • Nogre M; LFB Biotechnologies, Les Ulis, France.
  • Ferret C; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • de Marcos S; LFB Biotechnologies, Les Ulis, France.
  • Baptista L; LFB Biotechnologies, Les Ulis, France.
  • Drajac C; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • Mondon P; LFB Biotechnologies, Les Ulis, France.
  • De Romeuf C; LFB Biotechnologies, Les Ulis, France.
  • Rameix-Welti MA; Université Paris-Saclay, UVSQ, Inserm, Infection et inflammation, U1173, Montigny-Le-Bretonneux, France.
  • Eléouët JF; AP-HP, Hôpital Ambroise Paré, Laboratoire de Microbiologie, Boulogne-Billancourt, France.
  • Chtourou S; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • Riffault S; LFB Biotechnologies, Les Ulis, France.
  • Perret G; Université Paris-Saclay, INRAE, UVSQ, VIM, Jouy-en-Josas, France.
  • Descamps D; LFB Biotechnologies, Les Ulis, France.
Front Immunol ; 12: 683902, 2021.
Article in English | MEDLINE | ID: covidwho-1282386
ABSTRACT
Respiratory syncytial virus (RSV) is a public health concern that causes acute lower respiratory tract infection. So far, no vaccine candidate under development has reached the market and the only licensed product to prevent RSV infection in at-risk infants and young children is a monoclonal antibody (Synagis®). Polyclonal human anti-RSV hyper-immune immunoglobulins (Igs) have also been used but were superseded by Synagis® owing to their low titer and large infused volume. Here we report a new drug class of immunoglobulins, derived from human non hyper-immune plasma that was generated by an innovative bioprocess, called Ig cracking, combining expertises in plasma-derived products and affinity chromatography. By using the RSV fusion protein (F protein) as ligand, the Ig cracking process provided a purified and concentrated product, designated hyper-enriched anti-RSV IgG, composed of at least 15-20% target-specific-antibodies from normal plasma. These anti-RSV Ig displayed a strong in vitro neutralization effect on RSV replication. Moreover, we described a novel prophylactic strategy based on local nasal administration of this unique hyper-enriched anti-RSV IgG solution using a mouse model of infection with bioluminescent RSV. Our results demonstrated that very low doses of hyper-enriched anti-RSV IgG can be administered locally to ensure rapid and efficient inhibition of virus infection. Thus, the general hyper-enriched Ig concept appeared a promising approach and might provide solutions to prevent and treat other infectious diseases. IMPORTANCE Respiratory Syncytial Virus (RSV) is the major cause of acute lower respiratory infections in children, and is also recognized as a cause of morbidity in the elderly. There are still no vaccines and no efficient antiviral therapy against this virus. Here, we described an approach of passive immunization with a new class of hyper-enriched anti-RSV immunoglobulins (Ig) manufactured from human normal plasma. This new class of immunoglobulin plasma derived product is generated by an innovative bioprocess, called Ig cracking, which requires a combination of expertise in both plasma derived products and affinity chromatography. The strong efficacy in a small volume of these hyper-enriched anti-RSV IgG to inhibit the viral infection was demonstrated using a mouse model. This new class of immunoglobulin plasma-derived products could be applied to other pathogens to address specific therapeutic needs in the field of infectious diseases or even pandemics, such as COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / Immunization, Passive / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.683902

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin G / Immunization, Passive / Respiratory Syncytial Virus, Human / Respiratory Syncytial Virus Infections / Antibodies, Viral Type of study: Prognostic study Topics: Vaccines Limits: Animals / Humans Language: English Journal: Front Immunol Year: 2021 Document Type: Article Affiliation country: Fimmu.2021.683902