Nanobodies to multiple spike variants and inhalation of nanobody-containing aerosols neutralize SARS-CoV-2 in cell culture and hamsters.

The ongoing threat of COVID-19 has highlighted the need for effective prophylaxis and convenient therapies, especially for outpatient settings. We have previously developed highly potent single-domain (VHH) antibodies, also known as nanobodies, that target the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein and neutralize the Wuhan strain of the virus. In this study, we present a new generation of anti-RBD nanobodies with superior properties.

Is a universal influenza vaccine feasible?

The influenza virus causes significant human morbidity and mortality annually and poses a pandemic threat. In addition, the virus frequently mutates, contributing to thousands of identified strains. Current influenza vaccine solutions are strain specific, target existing strains, and achieve only approximately 40% vaccine effectiveness (VE).

Evaluating the immunogenicity and safety of a BiondVax-developed universal influenza vaccine (Multimeric-001) either as a standalone vaccine or as a primer to H5N1 influenza vaccine: Phase IIb study protocol.

Introduction: Influenza is a major respiratory viral infection of humans with high mortality and morbidity rates and profound economic impact. Although influenza vaccines are generally updated yearly to match the viruses expected in the coming season, genetic mutation and reassortment can result in unexpected novel strains. Therefore, it is important to develop universal vaccines inducing protective immunity to such strains before they appear.

Back to the future: Immunization with M-001 prior to trivalent influenza vaccine in 2011/12 enhanced protective immune responses against 2014/15 epidemic strain.

We previously reported a 2011/12 study in elderly showing that immunization with the universal influenza vaccine candidate, M-001, three weeks before administering trivalent influenza vaccine (TIV) enhanced seroconversion of Hemagglutination Inhibition (HAI) antibodies against known influenza vaccine strains circulating at that time. We now report that those subjects primed with M-001 prior to TIV in 2011 also showed, in their 2011 sera, significantly more HAI antibodies with improved seroprotection and seroconversion against strain A/Switzerland/9715293/2013(H3N2-like) that caused the 2014/15 influenza epidemic and that wasn't known to circulate in 2011/12. These data indicate that M-001 can provide broadened enhanced immunity extending even to influenza strains destined to circulate in future years.

Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population.

Background: A new vaccine, "Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine for the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in participants over 65 years old.

Epitope-based approaches to a universal influenza vaccine.

The development of vaccines has been one of the most important contributions of immunology to public health to date. Although several infectious diseases have all but vanished thanks to effective vaccines, the most common infectious disease, influenza, still represents a major threat to public health. This is more concerning than ever before in light of potentially virulent avian pandemic strains which have emerged in the last decade and infected human hosts, causing high morbidity and mortality.

Safety and immunogenicity of multimeric-001--a novel universal influenza vaccine.

Objective: A new vaccine, Multimeric-001, containing conserved linear epitopes from the HA, NP, and M1 proteins of influenza type A and type B strains was designed to protect against seasonal and pandemic influenza virus strains, regardless of mutations. We assessed its safety and tolerability and characterized humoral and cellular immune responses elicited by its administration.

Methods: Sixty healthy volunteers received either 250 or 500 μg injections, with or without adjuvant (Montanide ISA 51VG), or matching placebo.

Multimeric-001: BiondVax's universal flu vaccine. Interview by Duc Le.

Dr Tamar Ben-Yedidia has more than 15 years of experience in the field of immunology, with specific expertise in the development of vaccines. She started her career with Biotechnology General Ltd (BTG; Rehovot, Israel), working on the development of a recombinant hepatitis B vaccine. She joined the Weizmann Institute of Science (Rehovot, Israel) in 1994 and, under the auspices of Professor Ruth Arnon in the Department of Immunology, worked on the design of a peptide-based vaccine against several pathogens, focusing on influenza.

Preclinical efficacy of a virus-like particle-based vaccine against avian influenza H5N1.

Evaluation of: Kang S-M, Yoo D-G, Lipatov AS et al.: Induction of long-term protective immune responses by influenza H5N1 virus-like particles. PLoS ONE 4, e4667 (2009).

Epitope-based vaccine against influenza.

The currently available vaccines against influenza are viral strain specific and, hence, their efficacy is limited when the circulating strain is not the one included in them. We review herewith some of the more recently developed influenza vaccines and further describe our own data on the design of epitope-based broad-spectrum vaccine for human use. This vaccine is comprised of recombinant flagella that act as a carrier and adjuvant, expressing conserved epitopes of influenza proteins.

Towards an epitope-based human vaccine for influenza.

The conventional, currently available vaccines against influenza virus, though quite successful, suffer from a few shortcomings; one major limitation is their restriction to the specific strains that are included in the vaccine. We review herewith some of the more recently developed influenza vaccines and further describe our own results on the design of epitope-based vaccine for human use. In this vaccine, a combination of B- and T-cell epitopes are individually expressed within an immunogenic molecule--salmonella flagellin--and the resultant recombinant flagella serve both as a carrier and as an adjuvant.

A DNA aptamer prevents influenza infection by blocking the receptor binding region of the viral hemagglutinin.

Influenza A virus infection is a major source of morbidity and mortality worldwide. Current means of control for influenza are based on prophylaxis by vaccines and on treatment by the available specific influenza neuraminidase inhibitor drugs. The approach taken in the present study is to prevent and/or ameliorate influenza infection by site-specific blocking of the viral binding to host cell receptors.

Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK.

Transcriptional repression of E-cadherin, characteristic of epithelial to mesenchymal transition, is often found also during tumor cell invasion. At metastases, migratory fibroblasts sometimes revert to an epithelial phenotype, by a process involving regulation of the E-cadherin-beta-catenin complex. We investigated the molecular basis of this regulation, using human colon cancer cells with aberrantly activated beta-catenin signaling.

Old and new vaccine approaches.

The conventional, currently available vaccines, though quite successful, suffer from a few shortcomings which hamper future vaccine development. We present herewith some of the new approaches that are presently being pursued, including (1) the development of recombinant, or genetically engineered, vaccines which are based either on the expression of the relevant protective antigen and its formulation into vaccine, or the production of live vaccines, where an appropriate live vector (virus or bacterium) presents the foreign antigen. (2) The development of naked DNA vaccines that include the gene(s) coding for the relevant protective antigen(s).

A retro-inverso peptide analogue of influenza virus hemagglutinin B-cell epitope 91-108 induces a strong mucosal and systemic immune response and confers protection in mice after intranasal immunization.

In this study, a novel approach for the development of a peptide-based vaccine has been tested. We investigated the possibility of replacing an all-L amino acid peptide sequence corresponding to the protective B-cell epitope hemagglutinin (HA) 91-108 from influenza HA with a retro-inverso analogue encompassing this sequence. Retro-inverso peptides are composed of D-amino acids assembled in a reverse order from that of the parent L-sequence, thus maintaining the overall topology of the native sequence.

Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis.

beta-catenin and plakoglobin (gamma-catenin) are homologous molecules involved in cell adhesion, linking cadherin receptors to the cytoskeleton. beta-catenin is also a key component of the Wnt pathway by being a coactivator of LEF/TCF transcription factors. To identify novel target genes induced by beta-catenin and/or plakoglobin, DNA microarray analysis was carried out with RNA from cells overexpressing either protein.

Intranasal immunization with synthetic recombinant vaccine containing multiple epitopes of influenza virus.

The oligonucleotides coding for three epitopes (HA91-108, NP55-69, and NP 147-158) of influenza virus, stimulating B-cells, T-helper cells and cytotoxic T lymphocytes (CTLs), respectively, were previously employed for expressing each epitope in flagella that induced specific humoral and cellular immune responses. We have constructed new plasmids expressing all three epitopes as a single recombinant product. Two versions have been prepared-a longer one (Fla-HNN) comprising hybrid flagella containing the epitopes, and a shorter version (HNN).