RESUMEN
SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.
RESUMEN
Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.
Asunto(s)
Anticuerpos Neutralizantes/inmunología , Formación de Anticuerpos/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , SARS-CoV-2/inmunología , Toxoide Tetánico/química , Vacunas Conjugadas/administración & dosificación , Animales , COVID-19/inmunología , COVID-19/virología , Vacunas contra la COVID-19/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Vacunación , Vacunas Conjugadas/inmunologíaRESUMEN
Las vacunas combinadas permiten un grado de aceptación mayor entre la población, dado que se requiere de menos inmunizaciones para proteger contra las enfermedades infecciosas. Sin embargo, esto ha generado nuevos retos, ya que se han reportado numerosas interacciones entre los diferentes antígenos que conforman estas vacunas. El propósito del presente trabajo fue evaluar la interferencia potencial del componente pertussis de células completas sobre los ensayos para determinar la actividad biológica deotros antígenos como toxoide tetánico, Haemophilus influenzae tipo b (Hib) y hepatitis B. Para ello se estudiaron mediante ensayos de potencia vacunas combinadas que contenían estos antígenos y se compararon con vacunas monovalentes. A su vez se prepararonadyuvaciones experimentales cuya composición permitió estimar adecuadamente la extensión y naturaleza de la interacción entrecomponentes. Se obtuvo que el componente pertussis incrementó significativamente la actividad biológica de Hib y tétanos, aunque esto puede depender mucho del modelo animal y el diseño experimental utilizado. En cuanto al antígeno de hepatitis B se demostróque pertussis inhibía la potencia de este antígeno, tanto in vitro como in vivo, aunque por mecanismos diferentes y de forma no significativa(AU)
Combined vaccines have a higher level of acceptance in the population because fewer immunisations are required for protection against infectious diseases. Nevertheless, new challenges have appeared due to the report of some interference among the antigens included in such vaccines. The aim of this paper was to evaluate whole-cell Pertussis (wP) interference in potency tests with other antigens like tetanus, Haemophilus influenzae type b (Hib) and hepatitis B. For that purpose, we evaluated combined vaccines and compared them with the respective monovalent vaccines. Likewise, we prepared experimental formulations withdifferent antigen combinations to evaluate the extent and nature of the interference caused by wP. We obtained a significant increase of the tetanus and Hib biological activities when both antigens are combined with wP, although it depended on the animal model and the experimental design used. On the other hand, wP decreased both the in vivo and in vitro potency of HB in a non-significant way(AU)