Researchers from the Department of Microbiology and the State Key Laboratory of Emerging Infectious Diseases, LKS Faculty of Medicine, University of Hong Kong (HKUMed) conducted an in-depth study to identify an effective vaccine regimen to prevent nasal infection with SARS -CoV-2. The study demonstrated that a combination of intramuscular DNA receptor-binding domain (RBD) -based PD1 vaccine (PD1-RBD-DNA) and live attenuated intranasal influenza vaccine (LAIV-HK68-RBD) induced the strongest of the broadly neutralizing antibodies and resident memory CD8 T cells of the lungs, which prevented the live nasal challenges of SARS-CoV-2 in two animal models. The full research article is now online in the journal EBioMedicine published by The Lancet [link to the publication].
The COVID-19 pandemic has resulted in over 275 million infections with nearly 5.36 million deaths to date, but few vaccines approved for emergency use can induce sufficient mucosal protection to prevent nasal infection robust by SARS-CoV-2. Although the current vaccination has dramatically reduced the rates of hospitalization, severity and death, these vaccines are much less effective in preventing respiratory transmission of SARS-CoV-2, which has posed great challenges for pandemic control. . With the continued emergence of SARS-CoV-2 variants, including the rapid spread of the immune escape strain Omicron, there is an urgent need to discover a more effective vaccine strategy to block or reduce nasal transmission of SARS-CoV-2 .
Research methods and results
In this HKUMed study, significantly higher systemic and mucosal antibodies IgA / IgG and polyfunctional memory CD8 cells resident in the lungs were induced primarily by the heterologous combination regimen compared to current COVID-19 vaccination regimens. When two vaccinated mouse models were tested in the memory phase, 35 days after the second vaccination, the prevention of a robust SARS-CoV-2 infection in the nasal turbinate was achieved primarily by the heterologous combined diet. in addition to constant protection in the lungs. The new antibodies induced by the diet also neutralized many pandemic variants of the problems tested, including Alpha, Beta and Delta. The results provided proof of concept that robust mucosal immunity induced by the vaccine is needed to prevent nasal infection with SARS-CoV-2, which has significant implications for ending the COVID-19 pandemic. In progress.
Importance of the study
âThe results suggest that the clinical development of our two HKU vaccines remains a top priority to eliminate the uncontrolled spread of the COVID-19 pandemic. We are currently testing the nasal spray influenza vaccine and the DNA vaccine in humans, ânoted Professor Yuen Kwok-yung, Professor Henry Fok of Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed, who heads currently studying clinical trials of these two vaccines in Hong Kong.
âThe biggest challenge for the development of our COVID-19 vaccine is that we do not have a vaccine manufacturing facility in Hong Kong, which has delayed the translation of scientific findings into clinical use. Now, we are facing the same challenge after already manufacturing the Omicron Targeted DNA Vaccine for rapid clinical development, âsaid Professor Chen Zhiwei, Director of the AIDS Institute, Professor of the Department of Microbiology, HKUMed, who has co-directed the research.
“We believe that the use of nasal spray vaccination to strengthen the protection of the upper respiratory tract is the key strategy to reduce the transmission of SARS-CoV-2 and important for the ultimate control of the COVID-19 pandemic,” said Professor Chen Honglin, professor of the Department of Microbiology, HKUMed, who co-led the research.
About the research team
The research is co-led by Prof. Chen Zhiwei, Director of the AIDS Institute, and Prof. Chen Honglin, Department of Microbiology, HKUMed; and was conducted mainly by Dr Zhou Runhong, research officer; Dr Wang Pui, scientific manager; Dr Wong Yik-chun, former postdoctoral fellow; Mr. Xu Haoran, PhD student, Department of Microbiology, HKUMed, who shared first parentage. This team also includes Ms. Lau Siu-ying, technical manager; Dr Liu Li, assistant research professor; Dr Anna Zhang Jinxia, ââDr Bobo Mok Wing-yee, Scientific Officers; Dr Rachel Tam Chun-yee, Dr Zhou Dongyan, postdoctoral fellows; Ms. Peng Qiaoli and Ms. Liu Na, Mr. Deng Shaofeng, Mr. Zhou Biao, doctoral students; Mr. Chan Chun-yin, technical manager; Mr. Woo Kin-fai, Mr. Huang Haode, Mr. Du Zhenglong, Mr. Yang Dawei and Mr. Au Ka-kit, research assistants; Research assistant; and Professor Yuen Kwok-yung, Henry Fok Professor of Infectious Diseases and Chair of Infectious Diseases, Department of Microbiology, HKUMed.
The preclinical study was funded by the Hong Kong Research Grants Council – Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G), General Research Fund (17107019) and the Health and Medical Research Fund (19181052 and 19181012) the Food and Health Office of the Hong Kong Special Administrative Region government; Hong-Kong [emailÂ protected], Innovation and Technology Commission; and the Chinese National Key Research Project Program (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund. Professor Chen Zhiwei’s team was also partially supported by the Hong Kong Research Grants Council – Theme-Based Research Scheme (T11-706 / 18-N). GMP production of DNA vaccine and live attenuated influenza vaccine was supported by Shenzhen Science and Technology Program (JSGG20200225151410198) with matching funds from Shenzhen Immuno Cure BioTech Limited and Outbreak Response to novel coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations (CEPI), respectively.
About the Department of Microbiology, HKUMed
The academic staff of the Department of Microbiology are actively involved in clinical service and basic research. Postgraduate students can pursue studies in various aspects of microbiology and infectious diseases leading to a master’s or doctoral degree. The MSc program in Medical Sciences provides an opportunity for postgraduate students interested in further study of the biomedical aspects of clinical microbiology and infectious diseases. In addition, the Department’s clinical staff also participate in the training of clinical microbiologists in Hong Kong and Shenzhen. The Infectious Disease Courses and Graduate Diploma Program provide a unique avenue for the training of qualified infectious disease physicians.
To promote knowledge exchange, the research activities of the Department of Microbiology of HKUMed can be viewed at https://www.microbiology.hku.hk/.