Preclinical evaluation of a candidate naked plasmid DNA vaccine against SARS-CoV-2

New generation plasmid DNA vaccines may be a safe, fast and simple emergency vaccine platform for preparedness against emerging viral pathogens. Applying platform optimization strategies, we tested the pre-clinical immunogenicity and protective effect of a candidate DNA plasmid vaccine specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The DNA vaccine induced spike-specific binding IgG and neutralizing antibodies in mice, rabbits, and rhesus macaques together with robust Th1 dominant cellular responses in small animals. Intradermal and intramuscular needle-free administration of the DNA vaccine yielded comparable immune responses. In a vaccination-challenge study of rhesus macaques, the vaccine demonstrated protection from viral replication in the lungs following intranasal and intratracheal inoculation with SARS-CoV-2. In conclusion, the candidate plasmid DNA vaccine encoding the SARS-CoV-2 spike protein is immunogenic in different models and confers protection against lung infection in nonhuman primates. Further evaluation of this DNA vaccine candidate in clinical trials is warranted.

PANDEMIC AND “INFODEMIC”

Dear Reader, With the passage of about one year since the outbreak of the COVID-19 pandemic, huge amounts of scientific research data on COVID-19 are being generated daily and we have thus substantial information and understanding of the disease. While treatment with known anti-viral drugs, monoclonal antibodies, steroids and APIs continues, focus is now on the development and manufacturing of effective vaccines to protect the population at large. Several Indian companies are already conducting pan-India clinical trials of different vaccines. Bharat Biotech, in cooperation with the Indian Council of Medical Research and the National Institute of Virology, has developed a whole-virion inactivated vaccine on an inactivated platform, which will be administered intramuscularly in two doses (0, 28d). Biological E. is clinically evaluating its adjuvant protein subunit (RBD) vaccine on a protein subunit platform, again administered intramuscularly in two doses (0, 28d). Cadila Healthcare has developed a DNA plasmid vaccine on a DNA platform, administered intradermally in three doses (0, 28, 56d). Dr. Reddy’s Laboratories, together with the Russian Direct Investment Fund, will be conducting clinical trials of the Sputnik V adenovirus-based vaccine on non-replicating viral vector platform (developed by the Gamaleya National Research Institute). The Serum Institute of India, together with ICMR, is conducting clinical trials of the ChAdOx1-S AstraZeneca-Oxford vaccine on a non-replicating viral vector, also administered intramuscularly in two doses (0, 28d).

COVID-19: Recent advances in epidemiology, virology, etiopathogenesis, clinical trials and vaccine development

Background:The causative virus of COVID-19 has been named SARS-CoV-2. It is the seventh coronavirus that is pathogenic to humans and the third in the series of human pathogenic beta coronaviruses. Patient zero was identified to have contracted the virus in Wuhan, China. Shortly after the initial identification of the virus and its symptoms, multiple studies concluded that the virus originated from the “Wuhan seafood market”, a notorious market place for illegal wildlife trade based in Wuhan, a city in the Hubei region of the People’s Republic of China. Globally, as of 7:02 pm CEST, 29 May 2020, there have been 5704736 confirmed cases of COVID-19, including 357736 deaths, reported to the WHO. The transmission of COVID-19 is primarily by way of respiratory droplets, which can be developed via means of coughing or sneezing, hence spreading the disease from one person to another person. The research proposed indicates the possibility of bats as being the natural cistern of SARS-CoV-2, hence making COVID-19 a zoonotic disease. The most suspected intermediate host is the Malayan pangolin. SARS-CoV-2 is a single-stranded RNA virus that has an affinity for ACE2 receptors in humans, causing severe pathological symptoms. Symptoms like anorexia, dyspnea, fatigue, pyrexia, cough, headache, dizziness, nausea, productive sputum, abdominal pain, myalgia, sore throat, diarrhea, and vomiting. Vaccines that are currently in the clinical evaluation are the Adenovirus type 5 vector, mRNA-1273, Inactivated alum, ChAdOx, LNP-mRNA, DNA plasmid vaccine with electroporation and Inactivated vaccines. A Phase III randomized multicountry clinical trial comprising of 100 countries known as “Solidarity” (ISRCTN83971151) has been initiated by the WHO to achieve the unified goal of producing an adequate treatment for COVID-19. The present Solidarity trial focuses on the following drugs: Remdesivir, Lopinavir/Ritonavir with or without interferon beta-1a, Chloroquine, or hydroxychloroquine. Conclusion: It is invariably essential to promote research in this field of study and find an appropriate solution to the virus to allow individuals worldwide to lead a secure and healthy life.