Molecular protein design (steps): 
• Synthetic protein molecules will be designed with desired functions to meet practical needs in bio-medical and other fields. 
• The proteins will be designed based on available data from 3D-structures, chemistry, biology and medicine. 
• The engineered proteins will be constructed with DNA-recombination technologies and biochemical methodology. 
• The engineered proteins will be validated by fundamental characterizations by methods of biochemistry, biotechnology, oncology, and immunology, as well as by preclinical studies and clinical trials.  

Is antibody-dependent enhancement (ADE) a concern with vaccinations against COVID-19?

07/07/20 - SARS-CoV2 vaccine development

Antibodies against SARS-CoV2 are found in sera of people who have been infected. However, it has been reported that people who recovered from SARS-CoV2 infection are susceptible of second infections, indicating viral escape from immune responses with mechanisms possibly including (1) neutralization powers of the antibodies are weak and decay rapidly; or (2) the SARS-CoV2 commits mutations, changing its phenotypes of pathogenicity and immunogenicity. Therefore antibodies with high potency and breadth are required for fighting the current COVID-19 and oncoming coronaviral infections of SARS-CoV2 mutants and other strains.  

Spike protein (S protein) of SARS-CoV2, which mediates virus entry into host cells and is a major inducer of host immune responses. Therefore, recombinant S protein of SARS-CoV2 may serve as a platform for vaccine development. 

09/15/19 - HIV vaccine development

HIV Env: After three decades, development of HIV vaccine is still unsuccessful. The HIV envelop protein (Env) is a sole envelop protein of HIV particles, and therefore a focus of immunogenic research for developing neutralizing antibodies. 

There are three major obstacles preventing from success in using Env for HIV vaccine development. 
  1.  Glycan shield of Env: Dense glycans on the Env surface are considered “self” to humoral immune responses. 
  2.  Surface amino acid residues of Env mutate rapidly. 
  3.  Env structures (conformations) are unstable. Many forms of Env co-exist, including non-functional and functional forms. 

HIV anti-Env antibodies: There are three types of anti-Env antibodies, non-neutralizing antibodies, neutralizing antibodies, and broad neutralizing antibodies. 
  1.  Non-neutralizing antibodies: The native Env is a protein complex containing three gp120 and three gp41. These subunits dissociate from each other to form various non-functional forms, which are presumably more immunogenic than the native functional Env forms. Therefore, most anti-Env antibodies are the non-neutralizing antibodies elicited by the non-functional Env proteins. 
  2.  Neutralizing antibodies (nAbs) are the class of antibodies that only neutralize a specific HIV strain. 
  3.  Broad neutralizing antibodies (bnAbs) neutralize a broad spectrum of HIV strains and are current focuses on HIV vaccine research. bnAbs appear in a small number of individuals infected with HIV several years after infection via co-evolution between antibodies and HIV viral particles.
Methods of studying HIV bnAbs/vaccines: 
  1. Using single B-cell sorting and the second-generation DNA sequencing technologies to isolate bnAb lineages. Many bnAbs have been identified by this strategy. 
  2. Epitope-based methods: Many recombinant native-like Env proteins have been constructed; and Env epitopes have been discovered. The native-like Envs and the epitopes are used as immunogens in the efforts of developing HIV vaccines.  
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