HKU Bulletin May 2022 (Vol. 23 No. 2)

Current vaccines for SARS-CoV-2 have done well protecting people from severe illness and death, but some studies have shown that even vaccinated people may continue to carry quite high levels of the virus in their nose, a situation that may underlie asymptomatic transmission and re-infection. In response, HKU researchers have developed new vaccines that can address that problem and are both cheap and easy to manufacture. Professor Chen Honglin has drawn on his earlier work on a vaccine for influenza and coronaviruses to develop a nasal vaccine for COVID-19, while Professor Chen Zhiwei has adapted an HIV-AIDS vaccine he has been working on into an injectable COVID-19 vaccine. While work on their earlier vaccines is still going through the years-long process of pre-clinical and clinical trials, the urgency of COVID-19 has helped speed things up for the new vaccines and encouraged them to look at the effectiveness of combining the two. After multiple tests, they found that the injectable vaccine followed by a booster from the nasal vaccine could offer protection against the virus and reduce the viral load in the nose in animal trials. The findings were published late last year in The Lancet’s online journal EBioMedicine. “So far, this is the only vaccine combination able to block nasal infection and provide effective protection in both the upper and lower respiratory systems,” Professor Chen Honglin said. The nasal vaccine also has potential as a booster for people who have received Pfizer-BioNTech or other mRNA-based vaccines. Building expertise The origins of these vaccines date back two decades ago when, following the SARS outbreak in 2003, HKU began to build up expertise in infectious diseases. It is now a world leader in the field, hosting Post in April this year headlined, “The next leap in coronavirus vaccine development could be a nasal spray”. Professor Chen Zhiwei’s new vaccine is built on the model he developed for an HIV-AIDS vaccine. This DNA-based vaccine has been going through the conventional vaccine testing and approval process since 2013 and has a special way of delivering the antigen to antigenpresenting cells that induces potent antiviral immunity. For SARS-CoV-2, he swapped the HIV gene for the COVID-19 virus and has found that on its own, this vaccine can provide protection similar to that of mRNA vaccines while being cheaper and easier to manufacture. It can also be easily adapted to new variants. Hurdles to development The Lancet study reported on a variety of combinations using the two vaccines in animal models, with the best version being an injection among other things the State Key Laboratory of Emerging Infectious Diseases, which is led by Professor Chen Honglin and includes team member Professor Chen Zhiwei, who also is Director of the AIDS Institute at HKU. Before 2020, Professor Chen Honglin had been working on a vaccine candidate that showed potential for protection against both influenza and coronaviruses, by knocking out the NS1 gene from the NS segment in an influenza virus and inserting a receptor-binding-domain of the MERS (Middle East Respiratory Syndrome) coronavirus in its place. He quickly managed to replicate and insert SARS-CoV-2, which is also a coronavirus, and showed that it offered good protection against the virus. He also decided to focus on developing his findings into a nasal vaccine that provides ‘frontline’ protection where the virus can enter the body. Although a nasal form takes longer to develop than other vaccines, it is cheap and easy to deploy and has the potential to be a second-wave vaccine to boost immunity. There is also growing interest in this form of vaccine, as exemplified in an article in The Washington Researchers at HKU have been finding new ways to contain the COVID-19 virus and protect people from infection. Professor Chen Honglin and Professor Chen Zhiwei in the Medical Faculty have developed a novel vaccine strategy using an injection and nasal spray that may offer better protection and prevention against asymptomatic transmission of the virus. And engineers led by Professor Mingxin Huang have developed a new stainless steel that is COVID-resistant and effectively kills the virus. FIGHTING BACK AGAINST Professor Chen Honglin (left) has drawn on his earlier work on a vaccine for influenza and coronaviruses to develop a nasal vaccine for COVID-19. The nasal spray vaccine manufactured by Wantai BioPharm is currently in the third phase of trials in the Philippines, South Africa, Columbia and Vietnam. PROFESSOR CHEN HONGLIN So far, this is the only vaccine combination able to block nasal infection and provide effective protection in both the upper and lower respiratory systems. VACCINE BREAKTHROUGHS C VID-19 14 RESEARCH The University of Hong Kong Bulletin | May 2022 15

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