Modulation of the production of antibodies against respiratory viruses by neutralizing and secondary glycoproteins via TLR4.
Antibodies are key for the design of effective vaccines against respiratory viruses.
In this project, we describe the production and modulation of affinity maturation of antibodies by surface glycoproteins of respiratory syncytial virus (RSV), human metapneumovirus and influenza virus through interactions with Toll-like receptor 4 (TLR4).
The major neutralizing antigen in these respiratory virus antigen promotes and the antigen suppresses the production of antibodies through the modulation of this pattern recognition receptor (PRR) in mice.
The TLR4 effect affecting the B cell response was subsequently confirmed in infants infected with RSV, with two main alleles of the TLR4 gene in comparison to the heterozygots for the Asp299Gly/Thr399Ile (loss of function of TLR4 haplotype).
There is no vaccine to protect children against respiratory viruses. The selection of antigens for vaccines must consider the stimulation or inhibition properties of the individual glycoproteins through PRR for the production of antibodies.
The proteins of the different agents can act in trans as to affect responses against other pathogens.
These observations broadens our understanding of the phenomenon of interference antigen in vaccine preparations and provide new tools in order to improve the development of recombinant vaccines against these viruses.