bioRxiv Science⌕ Search

Biology subjects

Rosa, D. S.

Publications and source records attributed to Rosa, D. S..

2 recordsLinked to original sources

Anti-NS1 antibodies induced by immunization with dendritic cell targeted hybrid monoclonal antibodies do not induce platelet dysfunction.

Dengue fever causes a disease whose symptoms range from asymptomatic to more severe, that may even lead to death. During infection, the non-structural (NS) 1 protein is produced in infected cells and subsequently shed to the circulation. Anti-NS1 antibodies have been implicated in disease pathogenesis as well as in protection against lethal infection. Here we analysed the role of anti-NS1 antibodies elicited when the NS1 protein was specifically targeted to two distinct dendritic cell (DC) subsets by chimeric monoclonal antibodies (mAbs) that bind to the DC surface receptors DEC205 and DCIR2. BALB/c mice received two doses of DEC-NS1 or DCIR2-NS1 mAbs in the presence of an adjuvant. We observed that anti-NS1 antibodies induced by immunization with chimeric DEC-NS1 or DCIR2-NS1 mAbs did not cause significant pathology or were able to protect BALB/c mice from an intracranial DENV2 NGC strain challenge.

immunology↗

An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors' CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design

The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus.

immunology↗