Interleukin-2 (IL-2) engineered versions, with biased immunological functions, have emerged from yeast display and rational design. Here we reshaped the human IL-2 interface with the IL-2 receptor ...beta chain through the screening of phage-displayed libraries. Multiple beta super-binders were obtained, having increased receptor binding ability and improved developability profiles. Selected variants exhibit an accumulation of negatively charged residues at the interface, which provides a better electrostatic complementarity to the beta chain, and faster association kinetics. These findings point to mechanistic differences with the already reported superkines, characterized by a conformational switch due to the rearrangement of the hydrophobic core. The molecular bases of the favourable developability profile were tracked to a single residue: L92. Recombinant Fc-fusion proteins including our variants are superior to those based on H9 superkine in terms of expression levels in mammalian cells, aggregation resistance, stability, in vivo enhancement of immune effector responses, and anti-tumour effect.
•Introducing a domestic pneumococcal conjugate vaccine is likely to be cost-effective in Cuba.•In a ‘worst case’ scenario, cost per DALY averted was still less than 0.4 GDP per capita.•The impact of ...the vaccine would need to be monitored following its introduction.
To evaluate the cost-effectiveness of introducing a domestic pneumococcal conjugate vaccine (PCV7-TT) into the Cuban National Immunization Program (NIP).
We compared PCV7-TT given at two, four and six months of age to a scenario without PCV7-TT, over a ten-year period (2020–2029). We calculated the cost (Cuban pesos – CUP) per Disability Adjusted Life Year (DALY) averted from a Government perspective. We compared results from a static cohort model and a parsimonious prediction model informed by the serotype distribution among pneumococcal carriers and cases. We ran probabilistic and deterministic uncertainty analyses.
PCV7-TT could prevent 6897 (95% uncertainty interval, 4344–8750) hospitalizations and 189 (115–253) deaths in children <5 years of age, over the period 2020–2029. This could cost around 25 million (20–31) discounted CUP but would be offset by treatment cost savings of around 23 million (14–31). A parsimonious model predicted less favourable impact and cost-effectiveness but the cost per DALY averted was still less than 0.4 times the current GDP per capita.
PCV7-TT is likely to be cost-effective in Cuba. The impact of the vaccine would need to be carefully monitored following its introduction into the NIP.
SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer
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
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
OMVs is evaluated in vaccine candidates against SARS-CoV-2.
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.
Soberana01 is composed of the SARS-CoV-2 dimeric RBD and
Neisseria meningitidis
outer membrane vesicles (OMVs) adsorbed on alum. This vaccine induces a potent neutralizing immune response and shows potential against SARS-CoV-2 variants of concern.
PDF
