A quadrivalent recombinant influenza Hemagglutinin vaccine induced strong protective immune responses in animal models.

Globally, influenza poses a substantial threat to public health, serving as a major contributor to both morbidity and mortality. The current vaccines for seasonal influenza are not optimal. A novel recombinant hemagglutinin (rHA) protein-based quadrivalent seasonal influenza vaccine, SCVC101, has been developed. SCVC101-S contains standard dose protein (15µg of rHA per virus strain) and an oil-in-water adjuvant, CD-A, which enhances the immunogenicity and cross-protection of the vaccine. Preclinical studies in mice, rats, and rhesus macaques demonstrate that SCVC101-S induces robust humoral and cellular immune responses, surpassing those induced by commercially available vaccines. Notably, a single injection with SCVC101-S can induce a strong immune response in macaques, suggesting the potential for a standard-dose vaccination with a recombinant protein influenza vaccine. Furthermore, SCVC101-S induces cross-protection immune responses against heterologous viral strains, indicating broader protection than current vaccines. In conclusion, SCVC101-S has demonstrated safety and efficacy in preclinical settings and warrants further investigation in human clinical trials. Its potential as a valuable addition to the vaccines against seasonal influenza, particularly for the elderly population, is promising.

The E484K Substitution in a SARS-CoV-2 Spike Protein Subunit Vaccine Resulted in Limited Cross-Reactive Neutralizing Antibody Responses in Mice.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially emerging variants, poses an increased threat to global public health. The significant reduction in neutralization activity against the variants such as B.1.351 in the serum of convalescent patients and vaccinated people calls for the design of new potent vaccines targeting the emerging variant. However, since most vaccines approved and in clinical trials are based on the sequence of the original SARS-CoV-2 strain, the immunogenicity and protective efficacy of vaccines based on the B.1.351 variant remain largely unknown. In this study, we evaluated the immunogenicity, induced neutralization activity, and protective efficacy of wild-type spike protein nanoparticle (S-2P) and mutant spike protein nanoparticle (S-4M-2P) carrying characteristic mutations of B.1.351 variant in mice. Although there was no significant difference in the induction of spike-specific IgG responses in S-2P- and S-4M-2P-immunized mice, neutralizing antibodies elicited by S-4M-2P exhibited noteworthy, narrower breadth of reactivity with SARS-CoV-2 variants compared with neutralizing antibodies elicited by S-2P. Furthermore, the decrease of induced neutralizing antibody breadth at least partly resulted from the amino acid substitution at position 484. Moreover, S-4M-2P vaccination conferred insufficient protection against live SARS-CoV-2 virus infection, while S-2P vaccination gave definite protection against SARS-CoV-2 challenge in mice. Together, our study provides direct evidence that the E484K substitution in a SARS-CoV-2 subunit protein vaccine limited the cross-reactive neutralizing antibody breadth in mice and, more importantly, draws attention to the unfavorable impact of this mutation in spike protein of SARS-CoV-2 variants on the induction of potent neutralizing antibody responses.

A novel chloro-substituted pentenamide from the fruiting bodies of Amanita virgineoides.

One unusual chloro-substituted pentenamide, (3R)-4-chloro-3-hydroxy-4-pentenamide (1), together with 11 known compounds (2-12) were isolated from the fruiting bodies of Amanita virgineoides. The structure of 1 including the absolute configuration was characterized by extensive spectroscopic analyses and quantum calculation. Compound 1 displayed no obvious activity against herpes simplex virus (HSV), human enterovirus 71 (EV71) or coxsackievirus B3 (CVB3).

Anti-herpes simplex virus type 1 activity of Houttuynoid A, a flavonoid from Houttuynia cordata Thunb.

Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms. In this study, the anti-HSV-1 activity of Houttuynoid A, a new type of flavonoid isolated from H. cordata, was investigated. Three different assays confirmed that this compound could exhibit strong in vitro anti-HSV-1 activity. One assay verified that this compound could inhibit HSV-1 multiplication and prevent lesion formation in a HSV-1 infection mouse model. Mechanism analysis revealed that this compound could inactivate HSV-1 infectivity by blocking viral membrane fusion. Moreover, Houttuynoid A exhibited antiviral activities against other alpha herpes viruses, such as HSV-2 and varicella zoster virus (VZV). In conclusion, Houttuynoid A may be a useful antiviral agent for HSV-1.

Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin.

In recent years, enterovirus 71 (EV71) infections have caused an increasing epidemic in young children, accompanying with more severe nervous system disease and more deaths. Unfortunately, there is no specific medication for it so far. Here we investigated the anti-EV71 activity of chrysosplenetin and penduletin, two o-methylated flavonols isolated from the leaves of Laggera pterodonta. These two compounds were found to have strong activity in vitro against EV71 with low cytotoxicity. In the cytopathic effect (CPE) inhibition assays, both plaque reduction assay and virus yield inhibition assay, the compounds showed a similar 50% inhibitory concentration (IC(50)) value of about 0.20 µM. The selectivity indices (SI) of chrysosplenetin and penduletin were 107.5 and 655.6 in African green monkey kidney (Vero) cells, and 69.5 and 200.5 in human rhabdomyosarcoma (RD) cells, accordingly. The preliminary mechanism analysis indicates that they function not through blocking virus entry or inactivating virus directly but inhibiting viral RNA replication. In the time-of-addition assay, both compounds inhibited progeny virus production and RNA replication by nearly 100% when introduced within 4h post infection. In addition to EV71, both compounds inhibited several other human enteroviruses with similar efficacy. These findings provide a significant lead for the discovery of anti-EV71 drug.