Challenge against Covid-19: vaccine and immune memory
Last Updated 31 July, 2020. Cellspect Co., Ltd.
The dramatic emergence of SARS-CoV-2 into our lives and the subsequent COVID-19 pandemic have spawned the active development of nearly 200 vaccine candidates. Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and effective vaccine. The World Health Organization (WHO) continues to update COVID-19 candidate vaccine development progress. Currently, 6 vaccines are in clinical phase 3, 12 are in clinical phase 2 and 18 are in clinical phase 1. (Statistics as of July 30) 
In the past week, many exciting news have been released on the development of Covid-19 vaccines. Moderna, Inc. announced on July 26 to start the first large phase 3 trial including 30,000 participants.  The German company BioNTech has entered into collaborations with Pfizer and Fosun Pharma to develop their mRNA vaccine and on July 22, they announced the launch of a Phase 2/3 trial with 30,000 volunteers in the United States and other countries including Argentina, Brazil, and Germany. 
On the other hand, recent studies seem to paint a grim picture of how long COVID-19 immunity lasts, finding evidence of viral antibody counts plummeting in COVID-19 patients a mere two months after an initial infection. Some have worried that these people are vulnerable to reinfection and that long-lasting vaccines could be more difficult to develop, making widespread herd immunity impossible to obtain.
Although we still know too little about this virus and the time for research is too short, in fact, human immune memory is more than just antibodies and may be stronger than you think. An NIH review article summarizes well how immunological memory works.  The specific antibodies do not need to be present in large numbers when the body is no longer faced with a threat from the specific pathogen involved. Once the immune system's memory cells, such as T and B lymphocytes have been created, they can, usually, rapidly produce new specific antibodies, when and as needed. Furthermore, the immunological memory can also be established by NK cells. NK cells can respond to haptens or viruses, which results in generation of antigen-specific memory cells. Therefore, if there is a marked decrease in the number of specific Covid-19 antibodies, that does not mean that the body is incapable of mounting a rapid defense against re-infection from the Covid-19 virus. Rather, a decrease in the antibodies concerned can be just due to a lack of need. 
Scientists don't yet have data on long-term T-cells and memory B-cell response when it comes to SARS-CoV-2, but what they've seen so far is encouraging. Crotty, Sette and colleagues in June published a paper in the journal Cell looking at T-cell response in Covid-19 cases that did not require hospitalization. This study showed that in average cases of Covid-19, where people got sick but didn’t have to go to the hospital, basically all of them made a CD4+ T-cell (helper T-cell) and CD8+ T-cell (Killer T-cell) response. As for the persistence of memory B-cells, the authors still know much about it. But as we know B-cells generally seem to retain their memory for a long time (for years), the only way to answer it is to wait. 
Moreover, on July 20, the medical journal Lancet published two phase 1/2 clinical trial results of COVID-19 vaccine candidates. Both two vaccines have been proven safe for humans and produced strong immune reactions among patients. [6, 7] The first is from investigators at the Jenner Institute at Oxford University (Oxford, UK), with support from AstraZeneca, and the second from investigators supported by CanSino Biologics in Wuhan, China. Both groups used an adenoviral vector, and both report the vaccine achieving humoral responses to the SARS-CoV-2 spike glycoprotein receptor binding domain by day 28 as well as T-cell responses. Both report local and systemic mild adverse events such as fever, fatigue, and injection site pain. In neither trial was a severe adverse event reported.
Although these results are encouraging, nothing about this pandemic is simple. The wide spectrum of immune responses to the SARS-CoV-2 virus means that there will likely be a range of responses to a vaccine. Not everyone will receive the same level of protection from a given vaccine and some may not get any protection at all. What’s more, the immune response in older people is different from that in children, for example, so it’s hard to make a one-size-fits-all vaccine. The question of whether a vaccine will lead to effective immunity can only be answered with more clinical trials. One thing is that, COVID-19 antibodies may fade, but vaccine hopes will not.
1. World Health Organization: WHO: www.who.int
2. “Phase 3 clinical trial of investigational vaccine for COVID-19 begins” National Institutes of Health (NIH) press. July 26, 2020
3. “Pfizer and BioNTech Choose Lead mRNA Vaccine Candidate Against COVID-19 and Commence Pivotal Phase 2/3 Global Study”
Pfizer news. July 27, 2020
4. Weronika Ratajczak et al. June 30, 2018 “Immunological memory cells” Cent Eur J Immunol. 43(2): 194–203.
5. Alba Grifoni et al. June 25, 2020“Targets of T Cell Responses to SARS-CoV-2 Coronavirus in Humans with COVID-19 Disease and
Unexposed Individuals” Cell 181, 1489–1501
6. Pedro M Folegatti et al. July 20, 2020 “Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a
preliminary report of a phase 1/2, single-blind, randomised controlled trial” Lancet.
7. Zhu F-C et al, July 20, 2020 “Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in
healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial.” Lancet.
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