ABSTRACT
Intro The concept of training immunity originally developed for other diseases has gained attraction during the epidemic. Several clinical trials and epidemiological analyses of populations previously immunized with BCG and other vaccines were the focus of scientific discussions. Here we show the activation of innate immunity markers both at mucosal and systemic levels with a mucosal vaccine CIGB2020 (HeberNasvacTM) containing virus-like particles (HBsAg) and nucleocapsid particle (HBcAg) of the hepatitis B virus. Moreover, the immune potentiating capacity of the HBcAg combined with RBD protein was used to formulate a specific mucosal vaccine candidate against SARS-CoV-2 (MambisaTM). Methods With CIGB 2020 (100µg HBsAg and 100 µg HBcAg) were conducted two proof of concept trials in human volunteers and a Phase I-II open, randomized, and controlled trial in 46 volunteers older than 60 years, symptomatic or close contact of COVID-19 patients. The volunteers were randomly assigned to the treatment group or not treated group. The nasal spray was administered to the treatment group on days 0, 7, and 14 together with daily sublingual administrations. Mucosal and serum samples were collected on days 0, 4, and 8. With MambisaTM vaccine (50µg RBD and 40 µg HBcAg) was conducted one proof of concept trial and a Phase I-II open and randomized trial in 1131 volunteers 19 to 60 years old, evaluating three different devices for nasal administration. All the volunteers gave written informed consent. Findings CIGB2020 activates interferon-induced genes and TLR 3, 7, and 8 at the level of oropharyngeal mucosa and PBMC. Monocyte and lymphocyte populations were also activated. One dose of the MambisaTM vaccine induces high levels of specific IgG. The serum and mucosal antibodies show RBD-ACE2 binding inhibition capacity and neutralization activity. Conclusion Nasal immunization exhibits advantages in inducing immunity at the level of the nasopharyngeal mucosa in addition to the systemic response.