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Pharmacol Res ; 189: 106699, 2023 03.
Article in English | MEDLINE | ID: covidwho-2244141


Vaccination is considered one of the most successful strategies to prevent infectious diseases. In the event of a pandemic or epidemic, the rapid development and distribution of the vaccine to the population is essential to reduce mortality, morbidity and transmission. As seen during the COVID-19 pandemic, the production and distribution of vaccines has been challenging, in particular for resource-constrained settings, essentially slowing down the process of achieving global coverage. Pricing, storage, transportation and delivery requirements of several vaccines developed in high-income countries resulted in limited access for low-and-middle income countries (LMICs). The capacity to manufacture vaccines locally would greatly improve global vaccine access. In particular, for the development of classical subunit vaccines, the access to vaccine adjuvants is a pre-requisite for more equitable access to vaccines. Vaccine adjuvants are agents required to augment or potentiate, and possibly target the specific immune response to such type of vaccine antigens. Openly accessible or locally produced vaccine adjuvants may allow for faster immunization of the global population. For local research and development of adjuvanted vaccines to expand, knowledge on vaccine formulation is of paramount importance. In this review, we aim to discuss the optimal characteristics of a vaccine developed in an emergency setting by focusing on the importance of vaccine formulation, appropriate use of adjuvants and how this may help overcome barriers for vaccine development and production in LMICs, achieve improved vaccine regimens, delivery and storage requirements.

COVID-19 , Vaccines , Humans , Adjuvants, Vaccine , Pandemics , Vaccination/methods , Vaccines, Subunit , Adjuvants, Immunologic
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1397979


Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2. Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.

COVID-19 Vaccines/immunology , COVID-19/prevention & control , Protein Engineering/methods , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/genetics , Animals , Antibodies, Viral/immunology , Antigens, Viral , Binding Sites , COVID-19/virology , COVID-19 Vaccines/economics , Humans , Immunogenicity, Vaccine , Mice , Mice, Inbred BALB C , Models, Molecular , Protein Binding , Protein Conformation , Saccharomycetales/metabolism , Vaccines, Subunit