Anti-SARS-CoV-2 antibodies in a nasal spray efficiently block viral transmission between ferrets.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread in the population. We recently reported the production of bovine colostrum-derived antibodies that can neutralize the virus. These have been formulated into a nasal spray.

Crossprotection induced by virus-like particles containing influenza dual-hemagglutinin and M2 ectodomain.

To develop an effective universal vaccine against antigenically different influenza viruses. We generated influenza virus-like particles (VLPs) expressing the H1 and H3 antigens with or without M2e5x. VLP-induced immune responses and crossprotection against H1N1, H3N2 or H5N1 viruses were assessed to evaluate their protective efficacy.

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets.

Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity.

Influenza A virus resistance to 4'-fluorouridine coincides with viral attenuation in vitro and in vivo.

Pre-existing or rapidly emerging resistance of influenza viruses to approved antivirals makes the development of novel therapeutics to mitigate seasonal influenza and improve preparedness against future influenza pandemics an urgent priority. We have recently identified the chain-terminating broad-spectrum nucleoside analog clinical candidate 4'-fluorouridine (4'-FlU) and demonstrated oral efficacy against seasonal, pandemic, and highly pathogenic avian influenza viruses in the mouse and ferret model. Here, we have resistance-profiled 4'-FlU against a pandemic A/CA/07/2009 (H1N1) (CA09).

Intestinal microbiota programming of alveolar macrophages influences severity of respiratory viral infection.

Susceptibility to respiratory virus infections (RVIs) varies widely across individuals. Because the gut microbiome impacts immune function, we investigated the influence of intestinal microbiota composition on RVI and determined that segmented filamentous bacteria (SFB), naturally acquired or exogenously administered, protected mice against influenza virus (IAV) infection. Such protection, which also applied to respiratory syncytial virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was independent of interferon and adaptive immunity but required basally resident alveolar macrophages (AMs).

The detection of Toxoplasma gondii ME49 infections in BALB/c mice using various techniques.

Toxoplasma gondii infections are primarily diagnosed by serological assays, whereas molecular and fluorescence-based techniques are garnering attention for their high sensitivity in detecting these infections. Nevertheless, each detection method has its limitations. The toxoplasmosis detection capabilities of most of the currently available methods have not been evaluated under identical experimental conditions.

Comparing molnupiravir and nirmatrelvir/ritonavir efficacy and the effects on SARS-CoV-2 transmission in animal models.

Therapeutic options against SARS-CoV-2 are underutilized. Two oral drugs, molnupiravir and paxlovid (nirmatrelvir/ritonavir), have received emergency use authorization. Initial trials suggested greater efficacy of paxlovid, but recent studies indicated comparable potency in older adults.

Recombinant AMA1 Virus-like Particle Antigen for Serodiagnosis of Infection.

Toxoplasmosis diagnosis predominantly relies on serology testing via enzyme-linked immunosorbent assay (ELISA), but these results are highly variable. Consequently, various antigens are being evaluated to improve the sensitivity and specificity of toxoplasmosis serological diagnosis. Here, we generated virus-like particles displaying AMA1 of and evaluated their diagnostic potential.

Engineered Nanoparticulate Vaccines to Combat Recurring and Pandemic Influenza Threats.

Reoccurring seasonal flu epidemics and occasional pandemics are among the most severe threats to public health. Current seasonal influenza vaccines provide limited protection against drifted circulating strains and no protection against influenza pandemics. Next-generation influenza vaccines, designated as universal influenza vaccines, should be safe, affordable, and elicit long-lasting cross-protective influenza immunity.

Polycationic HA/CpG Nanoparticles Induce Cross-Protective Influenza Immunity in Mice.

The intranasal (i.n.) route is an ideal vaccination approach for infectious respiratory diseases like influenza.

Influenza NP core and HA or M2e shell double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.

Influenza viral infection causes acute upper respiratory diseases in humans, posing severe risks to global public health. However, current vaccines provide limited protection against mismatched circulating influenza A viruses. Here, the immune responses induced in mice by novel double-layered protein nanoparticles were investigated.

Skin vaccination with dissolvable microneedle patches incorporating influenza neuraminidase and flagellin protein nanoparticles induces broad immune protection against multiple influenza viruses.

We generated self-adjuvanted protein nanoparticles of conserved influenza antigens and immunized mice via skin vaccination with dissolvable microneedle patches (MNPs) to increase the strength and breadth of immune responses. We produced M2e nanoparticles via ethanol desolvation, and double-layered NA1/M2e (shell/core), NA1-FliC/M2e, NA2/M2e, and NA2-FliC/M2e protein nanoparticles by chemically crosslinking influenza NA and flagellin (FliC) onto the surfaces of the M2e nanoparticles. The resulting nanoparticles retained FliC TLR5 innate signaling activity and significantly increased antigen-uptake and dendritic cell maturation .

Double-Layered M2e-NA Protein Nanoparticle Immunization Induces Broad Cross-Protection against Different Influenza Viruses in Mice.

The development of a universal influenza vaccine is an ideal strategy to eliminate public health threats from influenza epidemics and pandemics. This ultimate goal is restricted by the low immunogenicity of conserved influenza epitopes. Layered protein nanoparticles composed of well-designed conserved influenza structures have shown improved immunogenicity with new physical and biochemical features.

Universal influenza vaccines: from viruses to nanoparticles.

Introduction: The current seasonal influenza vaccine confers only limited protection due to waning antibodies or the antigenic shift and drift of major influenza surface antigens. A universal influenza vaccine which induces broad cross-protection against divergent influenza viruses with a comparable or better efficacy to seasonal influenza vaccines against matched strains will negate the need for an annual update of vaccine strains and protect against possible influenza pandemics.

Areas Covered: In this review, we summarize the recent progress in nanoparticle-based universal influenza vaccine development.