Where to place our bet for COVID-19 treatment, vaccine or monoclonal antibodies?

Introduction

A gleam of light finally shone down on the global crisis of the prolonged battle against COVID-19, giving people hopes of preventive care and treatment in the near future by monoclonal antibodies against SARS-CoV-2. As stated the news of NIH’s phase III clinical trial, and another phase III trial by Regeneron in collaboration with National Institute of Allergy and Infectious Diseases, (Cohen, 2020a; Cohen, 2020b), we may anticipate a release of the preventive care in next couple of months.

COVID-19 vaccine and monoclonal antibodies development

Earlier this year, people put a lot of hopes on COVID-19 vaccine development as the ultimate solution for the pandemic. Although around 165+ players are in global vaccine race (Jonathan Corum, 2020), vaccine by its nature takes much longer than monoclonal antibody drugs to develop. Normal vaccine development usually takes years. For example, the Ebola vaccine takes 6 years to develop (Vaccine, 2020). The global community needs a quicker alternative since most of the world cannot afford a prolonged lockdown. Moreover, how to protect our health care professionals and essential workers brings the urgent need for immediate remedies. Monoclonal antibody therapy is a perfect option, yet it only got modest investments compared to that of vaccine development, thus jeopardize not only its progress but also the scale-up of trials and mass production to bring it to an affordable level and fulfill the huge needs. While the repetitive efforts have been made in vaccine development, which we still anticipate being no less than 12 -18 months in total, even in an expedited procedure, we need to consider carefully that the investment-return rate might be better for monoclonal antibodies at the global level.  Up to date, only 9 monoclonal antibodies are in clinical trials compared to >30 trials for vaccines (Biologics Tracker, 2020; Therapeutics tracker, 2020).

Why we should bet on COVID-19 monoclonal antibodies

Monoclonal antibodies have several advantages over vaccines. The development of monoclonal antibodies is relatively straightforward. Monoclonal antibodies can simply derive the sequences from patient antibody library, especially those neutralizing antibodies that can block virus entry via S1-RBD and ACE2 interaction, then select and engineer from this candidate pool that has been proven to be effective in nature, just as what has been done in previous SARS-CoV case (Jinye Liu, 2006). Vaccine candidates require prolonged test and trial process. No matter it is in the exploratory stage, preclinical stage, or clinical trials, vaccines involve the immune response that may take weeks per round and cannot be expedited. Monoclonal antibodies, on the other hand, only take several days to see their effects. If the first-round result is promising, then we can expand the scale of the trial. 6-8 years for vaccine clinical trial is typical, and it can easily stretch to 15 years. Although expedited, we still expect 1-2 years before the vaccine can truly kick-in to save us from the pandemic (Marovich, Mascola, & Cohen, 2020). However, the estimation of the launch of monoclonal antibodies is around Nov to Dec, which is still a relatively conservative estimation (Cohen, 2020a).

In terms of efficacy or side effects, no previous vaccines show 100% efficacy, and immune response to different pathogens remains case-by-case. Very little reliable information about SARS-CoV-2 immune response has been obtained to ensure the effectiveness of a vaccine, not to mention there are always immune-compromised people, mainly exist in the elderly population, may not react well on a vaccine. Monoclonal antibodies, especially neutralizing antibodies, provide passive immunity to people, regardless of an individual’s own immune system. Broadly neutralizing antibody drugs have been proved to be effective in HIV prevention and treatment (Rajesh Kumar, 2018).

Monoclonal antibodies are realistic options to achieve herd immunity until the formal launch of a safe,  effective, and scalable vaccine. Even though it may have limited production at the beginning stage after successful clinical trials, it can at least satisfy the needs to passive immunize healthcare professionals who constantly expose to the risk of infection, to help hospitalized COVID-19 patients alleviating their symptoms, and to prevent those essential workers from being infected. Studies of convalescent plasma therapy show promising results in past infectious diseases such as SARS, MERS, Influenza A, as well as COVID-19. Monoclonal is like an upgraded, scalable version, not to mention the monoclonal antibodies are pre-selected, designed, engineered, and strictly tested.

COVID-19 Monoclonal antibodies deserve more investments due to its benefits

No matter who wins the race, vaccine or monoclonal antibodies, we will need monoclonal antibodies anyway for immune-compromised people, especially elderly that are at high risk. Alleviate patient symptoms as a treatment is another benefit vaccine cannot offer. However, due to its limited investments, the production of monoclonal antibodies is still not very affordable.  This is also one of the reasons to ask more investments for monoclonal antibodies to help scale up the production and lower the cost so that it can be affordable for the global community. Several companies, including Lilly, AbCellera, AstraZeneca, GlaxoSmithKline, Genentech, and Amgen “jointly asked the U.S. Department of Justice (DOJ) whether they could share information about manufacturing their monoclonals without violating antitrust laws, “to expand and expedite production”  (Cohen, 2020a).

The investment-return of monoclonal antibody therapy is promising. Regardless of the pandemic, the global monoclonal antibodies therapy market size is $123.03 billion in 2019 with CAGR of 14%, twice the size and growth of vaccine market of  $41.7 billion in 2019 with CAGR of 7% (FBI, 2020; Markets, 2020).  In the case of the pandemic, the market size grows much more significantly. From a limited information source, COVID-19 vaccine investments are already over $8 billion to 6 different vaccines. In comparison, monoclonal antibodies only received $750 million from the government, which can hardly fulfill the needs of 40 million doses next year in the United States. 

The concerns for monoclonal antibody efficacy can be easily complemented by neutralizing antibody (NAb) test

The concerns for monoclonal antibodies involve the durability of passive immunity, which is not hard to resolve at all.  Simple monitoring of immunity durability by checking neutralizing antibodies’ efficacy can be scale up in a high-throughput matter in labs. A surrogate neutralizing antibody test, cPassTM test, produced by a biotech company GenScript located in New Jersey, USA, has got the HSA approval in Singapore and is seeking EUA approval in the United States, with clinical validation in multiple sites globally. The cPassTM test shows the perfect correlation with PRNT, the golden standard to measure neutralizing antibodies, but does not involve live viruses, and can be easily scaled up and get the results in less than an hour.  With the help of a surrogate neutralizing antibody test, we can easily evaluate when patients need the second dose to maintain their immunity (Min, 2020).   

Conclusion

Overall, monoclonal antibodies seem to be faster, promising solutions to restart the economy and do deserve more attention and investments. Besides prevention and treatment, they also provide indicators for evaluating a candidate vaccine. Looking back at the bets we placed on vaccine vs. monoclonal antibodies at such a critical point of fighting against COVID-19, it may not be too late to re-consider providing more supports for monoclonal antibodies development and trials. 

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