Our research objectives are:
We are currently studying
Understanding viral-host cell interactions is critical for treatment and prevention of infectious diseases
The immune response to viral infection comprises of the innate and adaptive responses. The adaptive response consists of cellular mediated response (T cell) and humoral (B cell or antibody-mediated) responses. Both responses are essential for antiviral defense and mediate immune memory response that is essential for rapid and efficient response to a subsequent encounter with a pathogen.
It is well established that neutralizing antibodies (nAbs) are key components in the protective immune responses to viral infections as they inhibit viral entry to host cells (for instance, by blocking the interactions with the host cell receptors or by preventing conformational changes required for viral entry). Consequently, nAbs can provide critical information on sites of vulnerability in the virus. Thus, a molecular-level understanding of viral neutralization by nAbs is imperative for the design of cross-protective vaccine antigens and the designing of cross-protective antiviral drugs.
Virus-host cell receptor interactions play a key regulatory role in the viral host range, tissue tropism, and viral pathogenesis. For envelope viruses, the binding of the virus to the host receptor can mediate conformational changes of the viral envelop proteins that trigger fusion of the virus membrane and cell membrane or endocytosis of the virus particle into the host cell. Understanding the envelope protein-receptor interactions can shade the light of the entry mechanism and viral tropism and advance the design of entry antivirals and prophylactic vaccines
Viral entry mechanism
The entry process of enveloped viruses into their host cells requires the fusion of the viral envelope with the host cell membrane, an orchestrated process driven by the interactions of viral envelope glycoproteins with receptors of host cells. Recent biochemical and structural studies have shed light on the entry mechanism of numerous enveloped viruses (e.g., HIV, influenza, Ebola), while for others (e.g., HCV) the entry mechanism is still unknown.
A deep understanding of the entry mechanism of these viruses is critical for controlling viral infection, and this knowledge can be applied to the development of therapeutics and prophylactic vaccines.
The Hepatitis C virus (HCV) is a major global health burden, having infected 1-2% of the world's population, resulting in ~500,000 deaths and an estimated 1.5-2 million new infections annually. Approximately 75-85% of HCV-infected people develop chronic infections that can lead to liver cirrhosis and, eventually, hepatocellular carcinoma. HCV is a major health concern in the Middle East, Central Asia, and Eastern Europe with a high estimated HCV prevalence (>3% of the population). In the US, HCV infection prevalence is approximately 1% with an unfortunate increase, since 2013, in the number of new infections. In Israel, the prevalence of HCV infection is approximately 1%.
Intense research over the past three decades has advanced our understanding of the HCV life-cycle and, inter alia, paved the way for the development of direct-acting antivirals (DAAs) that target non-structural proteins and effectively treat patients with persistent HCV infection. Nonetheless, DAA treatment faces several challenges e.g. late diagnostic, reinfections, DAA-resistant, and limited access to HCV diagnosis and treatment. In parallel, the rise of a new HCV-infected generation, a direct consequence of the current opioid epidemic that unfortunately shows no signs of slowing down, intensifies the concern of HCV distribution and underscores the critical need for the development of an effective vaccine for HCV eradication.
Diverse strategies for HCV vaccine development have been described; nevertheless, none has fully succeeded in eliciting a broad immune response, highlighting that alternative vaccination approaches are required to better control HCV spread. Understanding of HCV immune recognition and entry mechanism can pave the way for the design of improved subunit vaccine immunogens for better combatting HCV spread.
Hepatitis C virus
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in China at the end of 2019 and quickly spread to the vast majority of the world causing a global pandemic with a significant impact on global health, social behavior, geopolitics, and economy. SARS-CoV-2 is the third newly emerged coronavirus (CoV) that caused an outbreak in the past two decades (together with SARS-CoV and the middle east respiratory syndrome (MERS-CoV). The recurring outbreaks of new CoVs suggest that CoVs will continue to pose global health concerns highlighting the crucial need to develop a universal CoV vaccine.
The landscape of the immune responses against SARS-Cov-2 is still not fully clear. Clinical features and immunopathogenesis of SARS-CoV-2 pose similarities with SARS-CoV-1 and MERS-CoV, therefore, knowledge learned from previous CoVs infections has important implications for understanding the immune response against SARS-CoV-2. The immune response to SARS-CoV infections is associated with both innate and adaptive immune responses. The adaptive immune response consists of cellular (T cell) and humoral (B cell) responses with strong humoral immunity during the convalescent phase.
It is well established that neutralizing antibodies are key components in the protective immune responses to viral infections as they inhibit viral infection by, for instance, blocking the interactions with the host cell receptors or by preventing conformational changes required for viral entry. Cross-reactive mAbs can neutralize a wide spectrum of viral variants and can provide critical information about conserved epitopes on the viral structural proteins. Thus, a molecular-level understanding of CoVs neutralization by nAbs is imperative for the design of cross-protective vaccine antigens to elicit high levels of nAbs and for the designing of cross-protective antiviral drugs