Safety, immunogenicity and efficacy of Relcovax®, a dual receptor binding domain (RBD) and nucleocapsid (N) subunit protein vaccine candidate against SARS-CoV-2 virus.

SARS-CoV-2, severe acute respiratory syndrome coronavirus-2, causes coronavirus disease- 2019 (COVID-19). Mostly, COVID-19 causes respiratory symptoms that can resemble those of a cold, the flu, or pneumonia. COVID-19 may harm more than just lungs and respiratory systems. It may also have an impact on other parts of the body and debilitating effects on humans, necessitating the development of vaccines at an unprecedented rate in order to protect humans from infections. In response to SARS-CoV-2 infection, mRNA, viral vector-based carrier and inactivated virus-based vaccines, as well as subunit vaccines, have recently been developed. We developed Relcovax®, a dual antigen (Receptor binding domain (RBD) and Nucleocapsid (N) proteins) subunit protein vaccine candidate. Preliminary mouse preclinical studies revealed that Relcovax® stimulates cell-mediated immunity and provides broader protection against two SARS-CoV-2 variants, including the delta strain. Before conducting human studies, detailed preclinical safety assessments are required, so Relcovax® was tested for safety, and immunogenicity in 28-day repeated dose toxicity studies in rats and rabbits. In the toxicity studies, there were no mortality or morbidity, abnormal clinical signs, abnormalities in a battery of neurobehavioral observations, abnormalities in detailed clinical and ophthalmological examinations, or changes in body weights or feed consumption. In any of the studies, no abnormal changes in organ weights, haematology, clinical chemistry, urinalysis parameters, or pathological findings were observed. Immunogenicity tests on rats and rabbits revealed 100 % seroconversion. Relcovax® was therefore found to be safe in animals, with a No Observed Adverse Effect Level (NOAEL) of 20 µg/protein in rats and rabbits. In efficacy studies, Relcovax® immunised hamsters demonstrated dose-dependent protection against SARS-CoV-2 infection, with a high dose (20 µg/protein) being the most protective, while in cynomolgus macaque monkey study, lowest dose 5 µg/protein had the highest efficacy. In conclusion, Relcovax® was found to be safe, immunogenic, and efficacious in in vivo studies.

Pseudomonas aeruginosa: Infections and novel approaches to treatment "Knowing the enemy" the threat of Pseudomonas aeruginosa and exploring novel approaches to treatment.

Pseudomonas aeruginosa is an aerobic Gram-negative rod-shaped bacterium with a comparatively large genome and an impressive genetic capability allowing it to grow in a variety of environments and tolerate a wide range of physical conditions. This biological flexibility enables the P. aeruginosa to cause a broad range of infections in patients with serious underlying medical conditions, and to be a principal cause of health care associated infection worldwide. The clinical manifestations of P. aeruginosa include mostly health care associated infections and community-acquired infections. P. aeruginosa possesses an array of virulence factors that counteract host defence mechanisms. It can directly damage host tissue while utilizing high levels of intrinsic and acquired antimicrobial resistance mechanisms to counter most classes of antibiotics. P. aeruginosa co-regulates multiple resistance mechanisms by perpetually moving targets poses a significant therapeutic challenge. Thus, there is an urgent need for novel approaches in the development of anti-Pseudomonas agents. Here we review the principal infections caused by P. aeruginosa and we discuss novel therapeutic options to tackle antibiotic resistance and treatment of P. aeruginosa infections that may be further developed for clinical practice.