The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines
Abstract
mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.
Competing Interest Statement
Osaka University has filed a patent application for the enhancing antibodies. HA and YL are listed as inventors. HA is a stockholder of HuLA immune Inc.
https://www.biorxiv.org/content/10.1101/2021.08.22.457114v1?rss=1%22&utm_source=dlvr.it&utm_medium=tumblr
The Problem of Antibody-Dependent Enhancement
Before getting the vaccine, be sure you are aware of an immunopathology (immune disease) called “antibody-dependent enhancement.”
Definition and Explanation:
In reacting either to an infection or a vaccine, your body makes antibodies of various types to a variety of proteins on the surface of the virus. Some of the antibodies will be neutralizing, meaning that when they bind to the virus they prevent the virus from getting inside human cells. Other antibodies can likewise bind to the virus, but not make any difference to the virus’s successful functioning. These are non-neutralizing antibodies.
The problem is that both types of antibodies can also bind with loose viral proteins, especially from a vaccine, or a subsequent exposure to another virus, or with proteins of similar shape on or in human cells themselves. When antibodies bind to a loose protein, this triggers what’s called an immune complex reaction.
Immune complexes tend to deposit in certain parts of the body, such as the joints and kidneys. Antibody-Dependent Enhancement (ADE) appears to be a damaging inflammatory reaction of one’s own antibodies against one’s own tissues or cells, again, provoked by antibodies binding to one’s tissues or by immune complexes being deposited.
The antibody/antigen reaction triggers other inflammatory cells in a cascade effect, leading to tissue and organ damage which can be very serious.
https://rivercitymalone.com/health/covid-vaccine-the-problem-of-antibody-dependent-enhancement/