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.
ABSTRACT
Intro: With the first case of COVID-19 in Cuba on March 11, 2020, the Center for Genetic Engineering and Biotechnology in Havana began an extensive vaccine program. Two vaccines based on RBD recombinant protein were developed, one for systemic administration "Abdala" and one mucosal vaccine "Mambisa". Abdala received the EUA in July 2021 and "Mambisa" completed its clinical development as a booster dose for convalescent subjects. Method(s): Two doses (25 and 50 microg) and two schedules (0-14-28 and 1-28-56 days) were evaluated in phase I clinical trials with volunteers 19 to 54 years old. The phase II and III clinical trials were also double-blind, randomized, and placebo-controlled, and included respectively 660 and 48,000 volunteers from 19 to 80 years. The anti-RBD titers were evaluated using a quantitative ELISA system developed at the Center for Immunoassay, Havana Cuba, and ELECSYS system from Roche. The RBD to ACE2 plate-based binding competitive ELISA was performed to determine the inhibitory activity of the anti-RBD polyclonal sera on the binding of the hFc-ACE2 coated plates. The neutralization antibody titers were detected by a traditional virus microneutralization assay (MN50). Finding(s): The Abdala vaccine reached 92.28% efficacy. The epidemic was frankly under control in Cuba after the vaccine introduction having reached the highest levels of cases and mortality in July 2021 with the dominance of the Delta strain. The peak of the Omicron wave, unlike other countries, did not reach half of the cases of the Delta wave with a significant reduction in mortality. The mucosal vaccine candidate "Mambisa" completed its clinical development as a booster dose for convalescent subjects reaching the trial end-point. Conclusion(s): Vaccine composition based on RBD recombinant antigen alone is sufficient to achieve high vaccine efficacy comparable to mRNA and live vaccine platforms. The vaccine also protects against different viral variants including Delta and Omicron strains.Copyright © 2023