Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity

• DOI: 10.1126/scitranslmed.abn1413
• Publication Date: 2022-07-20T17:59:46Z
• Authors: Brittany L. Hartwell; Mariane B. Melo; Peng Xiao; Ashley A. Lemnios; Na Li; Jason Y.H. Chang; Jingyou Yu; Makda S. Gebre; Aiquan Chang; Laura Maiorino; Crystal Carter; Tyson J. Moyer; Neil C. Dalvie; Sergio A. Rodrigu...; Kristen A. Rodrigues; Murillo Silva; Heikyung Suh; Josetta Adams; Jane Fontenot; J. Christopher Love; Dan H. Barouch; Francois Villinger; Ruth M. Ruprecht; Darrell J. Irvine
• Keywords: Transcytosis

To combat the HIV epidemic and emerging threats such as SARS-CoV-2, immunization strategies are needed that elicit protection at mucosal portals of pathogen entry. Immunization directly through airway surfaces is effective in driving immunity, but poor vaccine uptake across mucus epithelial lining a limitation. The major blood protein albumin constitutively transcytosed bidirectionally epithelium interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate strategy “albumin hitchhiking” to promote immunity using an intranasal consisting immunogens modified amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted nasal mucosa mice nonhuman primates exhibited increased into tissue FcRn-dependent manner, leading enhanced germinal center responses nasal-associated lymphoid tissue. Intranasal amph-conjugated Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- 1000-fold higher antigen-specific IgG IgA titers serum, upper lower respiratory mucosa, distal genitourinary mucosae compared unmodified protein. Amph-RBD induced high SARS-CoV-2–neutralizing antibodies washes, bronchoalveolar lavage. Furthermore, amph-protein rhesus macaques 10-fold serum protein, supporting translational potential approach. These results suggest vaccines deliver antigen epithelia promising against HIV, other infectious diseases.