Saar Kuzi
Alessandra Coutinho Fernandes
William Cope
Richard Tapping
Kashif Ahmad
Reda Sadki
Shubhra Kanti Karmaker Santu
Adam P Rusch
Elle Meisner
Nereyda Ochoa
Landon J. Kunzelman
James DotimasFA16 Immunization Module’s Updates
6. Recent advances in vaccine technology
Respiratory syncytial virus (RSV) is one of the last remaining viruses that affect children and that has no vaccine yet. Estimates suggest that RSV cause 6.5% of deaths in children aged 1 month - 1 year of age, so it is an important vaccine to develop. Previously, a vaccine had been developed, but elicited an imbalanced Th2 response and low affinity antibodies, which caused enhanced disease after immunization. The same had been seen in the past in which inactivated measles virus vaccine caused enhanced disease upon natural infection with measles, most likely due to an imbalanced T cell response and ineffective neutralization with antibodies(1).
Therefore, a vaccine was designed to elicit an antibody which, when bound, inactivates RSV. This was done through protein crystallography and looking at epitope sites of a neutralizing peptide. They then used computational design to make a protein scaffold that would present those epitopes in that 3D structure. They then developed a plasmid that would encode that protein, and transfected E coli with it to make that protein that would present the neutralizing epitopes to the immune system, so that neutralizing antibodies could be generated. They found some success in animal models, but still need improvement (2).
Using crystallography and computational design to elicit a neutralizing antibody response would be a great idea to bring to multiple diseases. However, one would still need to find a neutralizing peptide through natural methods or high throughput screening, and also be able to develop the vaccine fast enough so that the neutralizing epitopes don't mutate or change shape. However, I still think this is a very interesting area to explore when developing vaccines.
(1) https://www.ncbi.nlm.nih.gov/pubmed/1609551
(2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107930/
@zheng Wang: Do you have any idea how immunization leads to enhanced disease? Is it related to the vaccines leading to an imbalanced Th2 cell response that stimulates IgE on mast cells?
@Preet Dhillon: I think that virus's can just mutate, which could change the shape of the virus and therefore also the epitopes that previous vaccines would protect against, like the flu.
@Carly Gridley: I think that some inactivated vaccines can cause enhanced disease (and are not used), but definitely not all of them.
It's very interesting to me that the inactivated vaccine enhances disease upon immunization. I followed up on the lack of a RSV vaccine and saw that there is a medicine that doctors can administer to high risk infants and children which I thought was interesting as well.
It's quite an interesting idea to apply the neutralizing peptide to other diseases. I didn't know though that the neutralizing epitopes mutate or change shape, which is a huge hurdle in their use. I wonder how/why the mutate and if there is a way to prevent or at least pro-long it.