In Hunt for Covid-19 Vaccine, Hong Kong University Researcher Calls for 'Rational' Approach

As the U.S. tops 140,000 coronavirus deaths, Chinese team explores potential shortcomings of vaccine approach targeting 'spike proteins.'

As the world has now well surpassed 14 million total known cases of Covid-19 and the U.S. has seen more than 3.7 million diagnoses -- some researchers are giving caution that a vaccine might not arrive as quickly and smoothly as first believed.  

Many are pinning hopes on a vaccine that could take advantage of the so-called "spikes" found on the surfaces of coronaviruses -- called "S proteins" -- that give them their pointy, or crown-like appearance. While the novel coronavirus discovered first in China last year is responsible for causing the disease Covid-19 -- other coronaviruses have been known to cause diseases such as SARS and MERS as well some types of common respiratory illnesses. The current belief is that by targeting the 'S proteins,' vaccine makers could create a shot that prevents the virus from latching onto human cells, halting the coronavirus' ability to reproduce.

But a recent study published in the life sciences journal "Cell Research" by Hong Kong and Chinese researchers raises some questions about that popular approach. The study analyzed and tested the immune response information from 39 coronavirus patients in Hong Kong to get a better idea of the feasibility of using the spike proteins to create a vaccine to prevent Covid-19.

Conducting the work were researchers at the University of Hong Kong's medical school, which started its own vaccine project; the Shenzhen Institutes of Advanced Technology; and Beijing University of Chemical Technology. 

TheStreet spoke with one of the lead researchers of the project, Jiandong Huang, a professor at the School of Biomedical Sciences at the University of Hong Hong's medical school, HKUMed, by email over the weekend to find out more about the findings and what they could mean for several of the vaccines under development for Covid-19, which Huang said "might be difficult to develop."

Following is a lightly edited version of the interview with Huang.

TheStreet: Did the introduction of SARS earlier in the the 2000s and the following vaccine research for that virus help pave the way for the current vaccine research for Covid-19 today? How so?

Huang: ....The research on SARS-CoV and MERS-CoV vaccines is helpful for Covid-19 vaccine development. The studies on SARS and MERS gave us a lot of knowledge common to coronaviruses.

Our team also started coronavirus research at that time. But due to the end of the outbreak and a decrease in funding support, most research weakened related basic research in the past few years. 

Now, several leading Covid-19 vaccine companies like Inovio  (INO) - Get Report, Sinovac (SVA) - Get Report, and CanSino Biologics (CASBF) have used techniques that were developed in that period.

TheStreet: Could you explain this concept discussed in your team's work, that the spike protein of the coronavirus is considered a promising antigen that could stimulate people's immune response against the disease, but that data of the immune response in patients are lacking. Does this mean vaccine some developers are going in the wrong direction?

Huang: For the development of vaccines, there are two strategies for all pathogens including SARS-CoV-2. One is the experience-based design, which might be applied for rapid development. Currently, most of the big-name companies or institutes are going this way. This experience-based approach is fast and will initiate clinical trials first, based on previous studies on other pathogens, before knowing possible side effects or effectiveness of the current one. Another is the rational design approach, which is a newly emerging strategy. This requires detailed understanding of the virus and importantly, human response to the infection. Our team is aiming to develop a predictable, safe, and effective vaccine based on solid in vivo and in vitro evidence.

TheStreet: On that idea of "rational" design, you have said "it is not ideal to construct a vaccine without selecting antigens. In the long run, an ideal vaccine should be designed rationally, which can generate neutralising antibodies only but not disease enhancing antibodies. It is better to avoid all useless antibodies." It sounds like you are concerned about some vaccine development that could help prevent Covid-19, but has side effects that could be a problem of their own. Is that correct?

Huang: All licensed vaccines are safe and effective after extensive tests, however, if the antigens used are not ideal, they will provoke the generation of many different antibodies. Only a fraction of the antibodies is actually useful to neutralize the virus. A majority of the antibodies cannot neutralize the virus. This is a huge "waste" of our immune resources at a minimum and, at worse, may be dangerous in some cases.... While the side effects of vaccines, or named adverse events following immunization, are rare, it could be fatal for some vaccinated individuals. Yet, for Covid-19, a large-scale vaccination for most people is necessary for prevention against the spreading of the SARS-CoV-2. In such a case, the careful selection of antigens or epitopes are important. (An epitope is a molecular area on the surface of an antigen that can trigger an immune response.) We are trying to develop a safe and effective vaccine that has removed all potential side effects at the designing stage.

TheStreet: Some studies are starting to show that people may lose their antibodies weeks or months after infection. Does this mean anything for vaccine development? Would it make them potentially less effective or would booster shots be needed?

Huang: Again, careful analysis of human responses is necessary to understanding what the loss of antibodies means. On the one hand, the protection could still be there due to the persistence of cellular immunity. On the other hand, it can very well mean that vaccination can last for a relatively short period. Vaccination with Covid-19 vaccine will stimulate different immune responses compared to (natural) infection of SARS-CoV-2. Extra measures in vaccination, including booster or the use of a special adjuvant to prolong the protection period are necessary. A long-term observation should be done in the clinical trials for the vaccinated population and infected population. Since the prime-boost strategy is a significant and an effective advance in the history of vaccinology, this has been utilized in almost all ongoing clinical trials for Covid-19.

TheStreet: If you can say, which vaccine production efforts now underway appear the most promising to you?

Huang: It is unclear before the phase 3 data has been released. For the Covid-19 vaccine, the rate of binding and neutralization titre is a key index to evaluate the safety and effectiveness of vaccine, as this index has been widely used in the respiratory syncytial virus vaccine. The lower rate we have, the more protective response we have. Of course, the vaccine with higher neutralization titre will be considered as a good candidate.

TheStreet: When do you see a safe vaccine reasonably being produced? Some people say within a year from now. Do you think that's possible? Why?

Huang: Only a vaccine validated in the phase 3 study will be licensed and launched. No one can know the effectiveness until it is fully tested in clinical trials. Since most of the current Covid-19 vaccines are being developed via the experience-based approach, the success is unpredictable.

(Note: TheStreet asked another scientist, Richard Ebright, a microbiologist at Rutgers University, who is unrelated to the study and Huang's research, for his perspective on this. Ebright agreed that "Huang is correct that vaccine development can be unpredictable and that, as a result, multiple approaches should be pursued in parallel," adding that multiple approaches are currently under investigation, including programs in China on "inactivated intact virus" vaccines, and programs in the the U.S., United Kingdom, European Union and China, focusing on the "S protein," as well as other types approaches, including peptide-targeted RNA vaccines, DNA vaccines and vectored vaccines.)

Information in this story has been updated, with quotes from Richard Ebright and clarification that of the dozens of vaccines under development, some are not using the same 'spike protein' approach discussed by Huang. Links have also been added.