10 research outputs found
LncRNA MALAT1 gene polymorphisms in coronary artery disease: A case-control study in a Chinese population
Engineered Nanovesicles Expressing Bispecific Single Chain Variable Fragments to Protect against SARS-CoV‑2 Infection
Coronavirus disease 2019 (COVID-19), caused by severe
acute respiratory
syndrome coronavirus 2 (SARS-CoV-2), has resulted in high morbidity
and mortality rates worldwide. Although the epidemic has been controlled
in many areas and numerous patients have been successfully treated,
the risk of reinfection persists due to the low neutralizing antibody
titers and weak immune response. To provide long-term immune protection
for infected patients, novel bispecific CB6/dendritic cell (DC)-specific
intercellular adhesion molecule 3-grabbing nonintegrin (SIGN) nanovesicles
(NVs) were constructed to target both the SARS-CoV-2 spike protein
(S) and the DC receptors for virus neutralization and immune activation.
Herein, we designed NVs expressing both CB6 and DC-SIGN single chain
variable fragments (scFvs) on the surface to block SARS-CoV-2 invasion
and activate DC function. Monophosphoryl lipid A (MPLA) was loaded
into the CB6/DC-SIGN NVs as an adjuvant to promote this process. The
CB6/DC-SIGN NVs prevented a pseudovirus expressing the S protein from
infecting the target cells expressing high levels of angiotensin-converting
enzyme 2 in vitro. Additionally, CB6/DC-SIGN NVs admixed with S-expressing
pseudoviruses activated the DCs, which was promoted by the adjuvant
MPLA loaded in the NVs. Using a mouse model, we also confirmed that
the CB6/DC-SIGN NVs effectively improved the neutralizing antibody
titer and inhibited the growth of tumors expressing the S protein
after 3 weeks of treatment. This potential NV-based treatment not
only exerts a blocking effect by binding the S protein in the short
term but may also provide patients with long-term protection against
secondary infections