RESUMEN
The emergence of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) variants and "anatomical escape" characteristics threaten the effectiveness of current coronavirus disease (COVID-19) vaccines. There is an urgent need to understand the immunological mechanism of broad-spectrum respiratory tract protection to guide broader vaccines development. In this study, we investigated immune responses induced by an NS1-deleted influenza virus vectored intranasal COVID-19 vaccine (dNS1-RBD) which provides broad-spectrum protection against SARS-CoV-2 variants. Intranasal delivery of dNS1-RBD induced innate immunity, trained immunity and tissue-resident memory T cells covering the upper and lower respiratory tract. It restrained the inflammatory response by suppressing early phase viral load post SARS-CoV-2 challenge and attenuating pro-inflammatory cytokine (IL-6, IL-1B, and IFN-{gamma}) levels, thereby reducing excess immune-induced tissue injury compared with the control group. By inducing local cellular immunity and trained immunity, intranasal delivery of NS1-deleted influenza virus vectored vaccine represents a broad-spectrum COVID-19 vaccine strategy to reduce disease burden.
RESUMEN
The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.
RESUMEN
Chronic hepatitis B (CHB) is often treated with drugs such as interferons and nucleoside (acid)/nucleotide (acid) analogs. While these drugs are effective in controlling the viral loads, they are not able to eliminate hepatitis B virus (HBV) from the body completely. Besides, side effects and drug resistance may by caused by the long-term use of these drugs. Several monoclonal antibodies (McAbs) against HBV, mostly against hepatitis B surface antigen (HBsAg), have been demonstrated with viral neutralization capability and with effective inhibition of HBV replication in relevant animal models. The use of a McAb individually or in combination with another therapy has the potentials to achieve functional cure of CHB. In this review, we summarized the encouraging results from the research and development of anti-HBV McAbs in clinical or pre-clinical development stage, aiming to provide new idea for the treatment of CHB.
RESUMEN
A safe and effective SARS-CoV-2 vaccine is essential to avert the on-going COVID-19 pandemic. Here, we developed a subunit vaccine, which is comprised of CHO-expressed spike ectodomain protein (StriFK) and nitrogen bisphosphonates-modified zinc-aluminum hybrid adjuvant (FH002C). This vaccine candidate rapidly elicited the robust humoral response, Th1/Th2 balanced helper CD4 T cell and CD8 T cell immune response in animal models. In mice, hamsters, and non-human primates, 2-shot and 3-shot immunization of StriFK-FH002C generated 28- to 38-fold and 47- to 269-fold higher neutralizing antibody titers than the human COVID-19 convalescent plasmas, respectively. More importantly, the StriFK-FH002C immunization conferred sterilizing immunity to prevent SARS-CoV-2 infection and transmission, which also protected animals from virus-induced weight loss, COVID-19-like symptoms, and pneumonia in hamsters. Vaccine-induced neutralizing and cell-based receptor-blocking antibody titers correlated well with protective efficacy in hamsters, suggesting vaccine-elicited protection is immune-associated. The StriFK-FH002C provided a promising SARS-CoV-2 vaccine candidate for further clinical evaluation.
RESUMEN
Objective To evaluate the immunostimulatory effects of polysaccharides, including Lycium barbarum polysaccharides ( LBP) , Angelica polysaccharides ( AP) , Licorice polysaccharides ( LP) and Inulin polysaccharides ( IP) , used alone or in combination with aluminum adjuvant on the recombinant protein of varicella-zoster virus (VZV) glycoprotein (gE) as an immunogen in mice. Methods BALB/c mice were randomly divided into 11 groups with five in each group. Intramuscular injection was given at Days 0 and 14. Serum samples were collected at weeks 0, 2, 3, 4 and detected for total anti-gE IgG titers and an-tibody subtypes by indirect ELISA. The mice were sacrificed at week 4 to collect spleen lymphocytes aseptic-ally. CCK-8 method was used to evaluate the proliferation of spleen lymphocytes. The levels of IFN-γ and IL-4 were measured by ELISA. The percentages of CD3+CD4+ and CD3+CD8+ T cell subsets were deter-mined by flow cytometry. Results The four plant-derived polysaccharides in combination with aluminum adjuvant showed good adjuvant activities. LP combined with aluminum adjuvant effectively increased the titer of IgG2, promote the proliferation of splenocytes and enhanced the secretion of IFN-γ and IL-4. Further-more, it also induced CD3+CD4+ and CD3+CD8+ T cell proliferation in vivo. Conclusions The four plant-derived polysaccharides in combination with aluminum adjuvant could all enhance antibody production. LP combined with aluminum adjuvant could induce cell-mediated immune responses, suggesting that it might be a promising adjuvant for varicella-zoster subunit vaccines.
