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Intranasal vaccination with lipid-conjugated immunogens promotes antigen transmucosal uptake to drive mucosal and systemic immunity.
Hartwell, Brittany L; Melo, Mariane B; Xiao, Peng; Lemnios, Ashley A; Li, Na; Chang, Jason Y H; Yu, Jingyou; Gebre, Makda S; Chang, Aiquan; Maiorino, Laura; Carter, Crystal; Moyer, Tyson J; Dalvie, Neil C; Rodriguez-Aponte, Sergio A; Rodrigues, Kristen A; Silva, Murillo; Suh, Heikyung; Adams, Josetta; Fontenot, Jane; Love, J Christopher; Barouch, Dan H; Villinger, Francois; Ruprecht, Ruth M; Irvine, Darrell J.
  • Hartwell BL; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Melo MB; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Xiao P; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Lemnios AA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Li N; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Chang JYH; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Yu J; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Gebre MS; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Chang A; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Maiorino L; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Carter C; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Moyer TJ; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Dalvie NC; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
  • Rodriguez-Aponte SA; Harvard Medical School, Boston, MA 02115, USA.
  • Rodrigues KA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Silva M; New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Suh H; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Adams J; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
  • Fontenot J; Consortium for HIV/AIDS Vaccine Development (CHAVD), Scripps Research Institute, La Jolla, CA 92037, USA.
  • Love JC; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Barouch DH; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Villinger F; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Ruprecht RM; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • Irvine DJ; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sci Transl Med ; 14(654): eabn1413, 2022 07 20.
Article in English | MEDLINE | ID: covidwho-1949951
ABSTRACT
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 mucosal immunity, but poor vaccine uptake across the mucus and epithelial lining is a limitation. The major blood protein albumin is constitutively transcytosed bidirectionally across the airway epithelium through interactions with neonatal Fc receptors (FcRn). Exploiting this biology, here, we demonstrate a strategy of "albumin hitchhiking" to promote mucosal immunity using an intranasal vaccine consisting of protein immunogens modified with an amphiphilic albumin-binding polymer-lipid tail, forming amph-proteins. Amph-proteins persisted in the nasal mucosa of mice and nonhuman primates and exhibited increased uptake into the tissue in an FcRn-dependent manner, leading to enhanced germinal center responses in nasal-associated lymphoid tissue. Intranasal immunization with amph-conjugated HIV Env gp120 or SARS-CoV-2 receptor binding domain (RBD) proteins elicited 100- to 1000-fold higher antigen-specific IgG and IgA titers in the serum, upper and lower respiratory mucosa, and distal genitourinary mucosae of mice compared to unmodified protein. Amph-RBD immunization induced high titers of SARS-CoV-2-neutralizing antibodies in serum, nasal washes, and bronchoalveolar lavage. Furthermore, intranasal amph-protein immunization in rhesus macaques elicited 10-fold higher antigen-specific IgG and IgA responses in the serum and nasal mucosa compared to unmodified protein, supporting the translational potential of this approach. These results suggest that using amph-protein vaccines to deliver antigen across mucosal epithelia is a promising strategy to promote mucosal immunity against HIV, SARS-CoV-2, and other infectious diseases.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: HIV Infections / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Scitranslmed.abn1413

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Full text: Available Collection: International databases Database: MEDLINE Main subject: HIV Infections / COVID-19 Topics: Vaccines Limits: Animals Language: English Journal: Sci Transl Med Journal subject: Science / Medicine Year: 2022 Document Type: Article Affiliation country: Scitranslmed.abn1413