PT  - JOURNAL ARTICLE
AU  - Farshad Guirakhoo
AU  - Lucy Kuo
AU  - James Peng
AU  - Juin Hua Huang
AU  - Ben Kuo
AU  - Feng Lin
AU  - Kevin Liu
AU  - Zhi Liu
AU  - Grace Wu
AU  - Shuang Ding
AU  - Lou-Liang Hou
AU  - Jennifer Cheng
AU  - Vicky Yang
AU  - Hank Jiang
AU  - Jason Wang
AU  - Tony Chen
AU  - WeiGuo Xia
AU  - Ed Lin
AU  - Chung Ho Hung
AU  - Kate Chen
AU  - Zhonghao Shih
AU  - Yilin Lin
AU  - Brandon T. Schurter
AU  - Mei Mei Hu
AU  - Gray Heppner
AU  - Delphine C. Malherbe
AU  - Alexander Bukreyev
AU  - Michael Hellerstein
AU  - Thomas Monath
AU  - Chang Yi Wang
TI  - A Novel SARS-CoV-2 Multitope Protein/Peptide Vaccine Candidate is Highly Immunogenic and Prevents Lung Infection in an Adeno Associated Virus Human Angiotensin-Converting Enzyme 2 (AAV hACE2) Mouse Model
AID  - 10.1101/2020.11.30.399154
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.30.399154
4099  - http://biorxiv.org/content/early/2020/11/30/2020.11.30.399154.short
4100  - http://biorxiv.org/content/early/2020/11/30/2020.11.30.399154.full
AB  - In this report, we describe the initial development and proof-of-concept studies for UB-612, the first multitope protein-peptide vaccine against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the pathogen responsible for the Coronavirus Disease of 2019 (COVID-19). UB-612 consists of eight components rationally designed for induction of high neutralizing antibodies and broad T cell responses against SARS-CoV-2: the S1-RBD-sFc fusion protein, six synthetic peptides (one universal peptide and five SARS-CoV-2-derived peptides), a proprietary CpG TLR-9 agonist, and aluminum phosphate adjuvant. Through immunogenicity studies in guinea pigs and rats, we optimized the design of protein/peptide immunogens and selected an adjuvant system, yielding a vaccine that provided excellent S1-RBD binding and high neutralizing antibody responses, robust cellular responses, and a Th1-oriented response at low doses of the vaccine. Our candidate vaccine was then advanced into challenge studies, in which it reduced viral load and prevented development of disease in a mouse challenge model and in nonhuman primates (NHP, immunogenicity part is completed, challenge is ongoing). A GLP-compliant toxicity study has shown a favorable safety profile for the vaccine. With the Phase 1 trial ongoing in Taiwan and additional trials planned worldwide, UB-612 is a highly promising and differentiated vaccine candidate for prevention of SARS-CoV-2 transmission and COVID-19 disease.Competing Interest StatementThe authors have declared no competing interest.