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Rabbit derived VL single-domains as promising scaffolds to generate antibody–dr...

André, Ana; Dias, Joana N. R.; Aguiar, Sandra I; Nogueira, Sara; Bule, Pedro; Carvalho, Joana; António, João P. M.; Cavaco, Marco; Neves, Vera

Antibody-drug conjugates (ADCs) are among the fastest-growing classes of therapeutics in oncology. Although ADCs are in the spotlight, they still present significant engineering challenges. Therefore, there is an urgent need to develop more stable and effective ADCs. Most rabbit light chains have an extra disulfide bridge, that links the variable and constant domains, between Cys80 and Cys171, which is not foun...


A prime-boost immunization strategy with vaccinia virus expressing novel gp120 ...

Calado, Rita; Duarte, Joana; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Martin, Francisco; Figueiredo, Inês; Almeida, Silvia; Luís, Graça

Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. M...


A Prime-Boost Immunization Strategy with Vaccinia Virus Expressing Novel gp120 ...

Calado, Rita; Duarte, Joana; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Martin, Francisco; Figueiredo, Inês; Almeida, Sílvia; Graça, Luis

Development of new immunogens eliciting broadly neutralizing antibodies (bNAbs) is a main priority for the HIV-1 vaccine field. Envelope glycoproteins from non-B-non-C HIV-1clades have not been fully explored as components of a vaccine. We produced Vaccinia viruses expressing a truncated version of gp120 (gp120t) from HIV-1 clades CRF02_AG, H, J, B, and C and examined their immunogenicity in mice and rabbits. M...


Novel peptides derived from dengue virus capsid protein translocate reversibly ...

Neves, Vera; Silva, Frederico Aires da; Morais, Maurício; Gano, Lurdes; Ribeiro, Elisabete; Pinto, Antónia; Aguiar, Sandra; Gaspar, Diana

The delivery of therapeutic molecules to the central nervous system is hampered by poor delivery across the blood-brain barrier (BBB). Several strategies have been proposed to enhance transport into the brain, including invasive techniques and receptor-mediated transport (RMT). Both approaches have several drawbacks, such as BBB disruption, receptor saturation, and off-target effects, raising safety issues. Her...


Antibody approaches to treat brain diseases

Neves, Vera; Silva, Frederico Aires da; Real, Sofia Corte; Castanho, Miguel A. R. B.

Recombinant antibodies are an emerging class of therapeutics with substantial promise to treat central nervous system (CNS) diseases such as Alzheimer's, Parkinson's, stroke, and brain cancers. However, poor blood–brain barrier (BBB) permeability hinders the progress of antibody therapies for conditions in which the target is located in the brain. Nonetheless, antibodies can nowa-days be engineered to enhance t...


Development of synthetic light-chain antibodies as novel and potent HIV fusion ...

Santos, Catarina Cunha; Figueira, Tiago N.; Borrego, Pedro; Oliveira, Soraia S.; Rocha, Cheila; Couto, Andreia; Cantante, Cátia; Costa, Quirina Santos

OBJECTIVE: To develop a novel and potent fusion inhibitor of HIV infection based on a rational strategy for synthetic antibody library construction. DESIGN: The reduced molecular weight of single-domain antibodies (sdAbs) allows targeting of cryptic epitopes, the most conserved and critical ones in the context of HIV entry. Heavy-chain sdAbs from camelids are particularly suited for this type of epitope recogni...


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