A Nanoparticle Comprising the Receptor-Binding Domains of Norovirus and as a Combination Vaccine Candidate.

Background: Noroviruses, which cause epidemic acute gastroenteritis, and parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P NP).

Pseudovirus nanoparticles targeting the receptor binding HA1 domains of influenza viruses elicited high HA1-specific antibody responses and protected mice against mortality caused by influenza virus challenges.

The continually high disease burden of influenza and the relatively low effectiveness of current influenza vaccines call for enhanced vaccine strategies. We previously generated unique S-HA1 pseudovirus nanoparticles (PVNPs) displaying the receptor binding HA1 antigens of the H7N9 subtype as an influenza vaccine candidate and characterized their features in biochemistry, biophysics, structure, and immune response. In this follow up study, we created new S-HA1 PVNPs displaying the HA1 antigens of other common influenza viruses, including two H1N1 strains, one H3N2 strain, and an influenza B virus, respectively.

A Pseudovirus Nanoparticle Displaying the Vaccinia Virus L1 Protein Elicited High Neutralizing Antibody Titers and Provided Complete Protection to Mice against Mortality Caused by a Vaccinia Virus Challenge.

The recent worldwide incidence of mpox infection and concerns about future emerging variants of mpox viruses highlight the need for the development of a new generation of mpox vaccines. To achieve this goal, we utilized our norovirus S nanoparticle vaccine platform to produce and evaluate two pseudovirus nanoparticles (PVNPs), S-L1 and S-J1. These PVNPs displayed the L1 neutralizing antigen target of the vaccinia virus and a yet-untested J1 antigen of the mpox virus, respectively, with the aim of creating an effective nanoparticle-based mpox vaccine.

Cryo-EM structures of cotton wool plaques' amyloid β and of tau filaments in dominantly inherited Alzheimer disease.

Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs.

Cryo-EM structures of amyloid-β and tau filaments in Down syndrome.

Adult individuals with Down syndrome (DS) develop Alzheimer disease (AD). Whether there is a difference between AD in DS and AD regarding the structure of amyloid-β (Aβ) and tau filaments is unknown. Here we report the structure of Aβ and tau filaments from two DS brains.