Mass vaccination of the population worldwide to eradicate COVID-19 infection requires more effective coronavirus vaccines than are currently available. Clinical trials of two more vaccines show encouraging intermediate results.
The Doctors of the Therapeutic Clinic of the Medical School of the National and Kapodistrian University of Athens, Theodora Psaltopoulou, Giannis Danasis, Maria Gavriatopoulou and Thanos Dimopoulos (Rector of EKPA) summarize the preliminary results of the study of phase Phase 1-226 of embol Johnson recently published in The New England Journal of Medicine.
The Ad26.COV2.S vaccine is a recombinant vaccine that uses an inactivated adenovirus (serotype 26 – Ad26), which cannot be amplified but encodes and expresses the S protein protein spike of the SARS-CoV-2 virus. This is a multicenter study in which healthy adult volunteers aged 18-55 (group 1) and 65 years and older (group 3) received the Ad26.COV2.S low or high dose or placebo vaccine.
The volunteers received the vaccine in either one or two doses. The primary endpoints of the study were safety and immunogenicity. Following the first dose in 805 volunteers in groups 1 and 3 and the second dose in group 1, the most common side effects included diarrhea, headache, myalgia and pain at the injection site. The most common systemic side effect was fever. Systemic side effects were less common in group 3 (single dose) than in group 1 (two doses) and in those receiving the low dose of the vaccine compared with those receiving the high dose of the vaccine.
Neutralizing antibody titer to SARS-CoV-2 was detected in at least 90% of participants on day 29 after the first dose, and rose to 100% by day 57 with a further increase in their titer, regardless of dose or age group. Antibody titers remained stable until at least day 71. The second dose led to an increase in the titer of neutralizing antibodies. The antibody response to the S protein of SARS-CoV-2 was similar to the immune response to neutralizing antibodies. On day 14, specific T-lymphocytes were detected in 76-83% of patients in group 1 and 60-67% in group 3, with a clear shift to helper T-type lymphocytes. A significant response was also observed to generate a T-lymphocyte response. .
In conclusion, the results regarding the safety and immunogenicity of the Ad26.COV2.S vaccine are highly encouraging and support further evaluation of the vaccine in phase 3 clinical trials.
New mRNA vaccine that does not need a second dose
A new mRNA vaccine for the new coronavirus, which does not require a second dose, has received the green light to begin Phase 2 clinical trials in the US and Singapore. The ARCT-021 vaccine is developed by Arcturus Therapeutics, a pharmaceutical company specializing in the development of drugs and vaccines using mRNA technology.
Phase 2 licensing of its clinical trials in the US was granted by the US Food and Drug Administration (FDA). Its provisional data is expected within the first months of 2021, with Phase 3 scheduled to begin in the second quarter of the year. In this case, the company will be able to apply for approval under conditions (Emergency Use Authorization, Emergency Use Authorization) in the second half of the year.
In Singapore, the Health Sciences Authority (HSA) evaluated the same data with the FDA. Approved Phase 2 of the study, as data from Phase 1/2 of the study showed that the ARCT-021 vaccine is well tolerated, while causing humoral and cellular immunity (immunogenicity).
The Arcturus Therapeutics ARCT-021 vaccine is very low dose and completely free of any viral material: virus free, virus free, and no adjuvants. It is produced by a mRNA replication and replication technology (STARR τεχνο technology), which is then released into the body through an innovative lipid system (LUNAR® system), both of which are owned by Arcturus.
A single, very low dose (only 5 micrograms – μg) elicits a significant T-cell immune response (high levels of T-lymphocytes, which are crucial for protection against COVID-19). The T-cell response is important because:
T-lymphocytes are much better associated than antibodies with protective coronavirus immunity.
High T-cell levels in patients with SARS and MERS were associated with better outcomes than high antibody levels.
T-lymphocytes for the new coronavirus provide cross-reactivity with various coronaviruses, including those that cause the common cold (winter “viruses”).
T-lymphocytes are like adult stem cells: they can remain dormant for years in low numbers, like soldiers resting on the battlefield, ready to be activated at the slightest sign of trouble.
The ARCT-021 vaccine has a very promising safety profile, with a single dose of less than 10 μg, while other mRNA vaccines require higher doses (60-200 μg) with two injections.
The ARCT-021 vaccine is also easy to store and distribute. It will be shipped and stored in a vial as a dry solid powder (produced by the lyophilization method) and not as a frozen liquid. Therefore no extreme cooling conditions or dry ice handling will be required.
The fact that the ARCT-021 vaccine will potentially be administered in a single dose simplifies its administration. In addition, published data from animal model studies have shown that it provides 100% protection with a single dose.
Israel and Singapore have already reached agreements on the supply of the vaccine after the end of clinical trials, while Arcturus is in contact with other governments of various countries.