RESEARCH PROJECTS
POLYREACTIVITY
We typically define antibodies by the antigens they stick to: if you get the flu, you make flu antibodies; or, if you get the COVID vaccine, you get COVID antibodies. But what happens when an antibody sticks to multiple distinct antigens?
This phenomenon is called polyreactivity, and, because of its correlation with autoreactivity (Bajic, 2019), it might pose a problem for universal flu vaccine engineers who are looking to target conserved epitopes of flu hemagglutinin. It has been found that the B-cell repertoire of antibodies that target these regions is overwhelmingly polyreactive (Guthmiller, 2020). So, we ask the question: are polyreactive antibodies expressed in the serum?
Using IgSeq and many (many) ELISAs, we are sequencing serum antibodies and characterizing their polyreactivity, as well as their binding epitopes, to get a better picture of what antibodies are actually expressed.
However, we have run into one major problem: what defines polyreactivity?
The literature is incredibly vague about what constitutes a polyreactive antibody, and antibodies have historically only been screened against a dozen or so antigens. In a universe with many potential antigens, can any one antibody be deemed as non-polyreactive because it doesn’t stick to twelve? And what level of binding counts as polyreactive? If a strong flu antibody binds weakly to nucleic acids, is it polyreactive, even if it doesn’t have any measurable biological effect?
To better understand polyreactivity, we propose the using linear peptide arrays. These chips, laid out with 5500 random 15-mers, are helping us better characterize binding patterns of polyreactive antibodies. Using both our ELISAs and these arrays, we hope to better define what a polyreactive antibody looks like.
NEURAMINIDASE
Another potential target being explored in the realm of universal flu vaccines is neuraminidase (NA). NA is the second of two major flu surface proteins, and it is the main target in most flu antivirals due to its conserved active site. However, it has historically been neglected in flu vaccine development in favor of its sister hemagglutinin (HA).
Though NA has been included in flu vaccines, the quality control has been lacking to the point that even inactivated vaccines don’t induce an immune response to NA, whereas natural infection sometimes induces a greater response to NA than HA, particularly in H3N2 infections.
However, these studies have investigated only the B-cell repertoire, and it is unknown how the serum repertoire actually responds to NA and if it is a viable target for a universal flu vaccine.
So far, I have run IgSeq on one donor and identified several anti-NA antibodies that I will be characterizing by binding epitope moving forward.
MEDIA
