Phosphate-mediated coanchoring of RBD immunogens and molecular adjuvants to alum potentiates humoral immunity against SARS-CoV-2

Kristen A Rodrigues; Sergio A Rodriguez-Aponte; Neil C Dalvie; Jeong Hyun Lee; Wuhbet Abraham; Diane G Carnathan; Luis E Jimenez; Julia T Ngo; Jason Y H Chang; Zeli Zhang; Jingyou Yu; Aiquan Chang; Catherine Nakao; Benjamin Goodwin; Christopher A Naranjo; Libin Zhang; Murillo Silva; Dan H Barouch; Guido Silvestri; Shane Crotty; J Christopher Love; Darrell J Irvine

doi:10.1126/sciadv.abj6538

Phosphate-mediated coanchoring of RBD immunogens and molecular adjuvants to alum potentiates humoral immunity against SARS-CoV-2

Sci Adv. 2021 Dec 10;7(50):eabj6538. doi: 10.1126/sciadv.abj6538. Epub 2021 Dec 8.

Authors

Kristen A Rodrigues^{1

2

3

4}, Sergio A Rodriguez-Aponte^{1

5}, Neil C Dalvie^{1

6}, Jeong Hyun Lee^{4

7}, Wuhbet Abraham^{1

3}, Diane G Carnathan^{4

8

9}, Luis E Jimenez^{8

9}, Julia T Ngo^{8

9}, Jason Y H Chang^{1

3}, Zeli Zhang^{4

7}, Jingyou Yu¹⁰, Aiquan Chang^{10

11}, Catherine Nakao⁷, Benjamin Goodwin⁷, Christopher A Naranjo¹, Libin Zhang^{1

3}, Murillo Silva^{1

3

4}, Dan H Barouch^{3

10}, Guido Silvestri^{4

8

9}, Shane Crotty^{4

7}, J Christopher Love^{1

6}, Darrell J Irvine^{1

3

4

5

12

13}

Affiliations

¹ Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
² Harvard-MIT Health Sciences and Technology Program, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
³ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02139, USA.
⁴ Consortium for HIV/AIDS Vaccine Development, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁵ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁶ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
⁷ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
⁸ Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322, USA.
⁹ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
¹⁰ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
¹¹ Harvard Medical School, Boston, MA 02215, USA.
¹² Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹³ Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

There is a need for additional rapidly scalable, low-cost vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to achieve global vaccination. Aluminum hydroxide (alum) adjuvant is the most widely available vaccine adjuvant but elicits modest humoral responses. We hypothesized that phosphate-mediated coanchoring of the receptor binding domain (RBD) of SARS-CoV-2 together with molecular adjuvants on alum particles could potentiate humoral immunity by promoting extended vaccine kinetics and codelivery of vaccine components to lymph nodes. Modification of RBD immunogens with phosphoserine (pSer) peptides enabled efficient alum binding and slowed antigen clearance, leading to notable increases in germinal center responses and neutralizing antibody titers in mice. Adding phosphate-containing CpG or saponin adjuvants to pSer-RBD:alum immunizations synergistically enhanced vaccine immunogenicity in mice and rhesus macaques, inducing neutralizing responses against SARS-CoV-2 variants. Thus, phosphate-mediated coanchoring of RBD and molecular adjuvants to alum is an effective strategy to enhance the efficacy of SARS-CoV-2 subunit vaccines.

Abstract

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