The ins and outs of the Rhinovirus!
Updated: Jan 15, 2020
Just as millions of other people around the globe, I recently suffered through a few days of the common cold. Last year I remember hearing about an update of a universal rhinovirus vaccination that could protect us from getting future colds! Wouldn't that be great! So I thought I would write my first 500 word review on the topic. Here we go!
Rhinoviruses (RVs) are non-enveloped RNA viruses that belong the picornaviridae family. The single strand RNA genome consists of approximately 7500 basepairs and codes for 11 different proteins. There are three main species of rhinoviruses, simply termed A, B, and C. This virus has four main structural proteins: viral protein (VP) 1-4. VP1-3 are found on the outer capsid, while VP4 is an internal protein that is involved with RNA assembly. The protein capsid of the RV consists of 60 proteins.
A serotype is a specific group of viruses within a species of virus that has distinct characteristics. As of 2017 there have been 83 HRV-A, 32 HRV-B and 55 HRV-C types of RV identified, although there could be as many as 170 different types that circulate.
Viral entry is mediated by VP1 on the surface of the capsid. A majority of RV utilize intercellular adhesion molecule 1 (ICAM-1) for cellular entry, while a smaller subset of RV can enter the cell through low-density lipoprotein receptor (LDLR). Within the last 5 years another receptor, cadherin-related molecule 3 (CDHR3) has been identified as the receptor used by HRV-C types.
Current status of RV vaccination
Many people get colds multiple times a year, yet we do not seem to be protected from new RV infections. One of the features of immunological memory is that the immune system can recognize, and “remember” certain features, or antigens, of the pathogens we come in contact with.
As mentioned previously, there are well over 150 distinct types of RV that circulate throughout the population. Research has shown that there limited immunological protection across different RV types, which also poses another issue. For a vaccination to be effective against all rhinoviruses we could come in contact with, the vaccine would need to be designed such that is has features that are present on all of the RVs.
Studies for RV vaccination began in the early 1960s, and much progress has been made since then. Genomic and proteomic information is now available for the different RV serotypes such that structurally similar components between types can be identified. Within the last 10 years, conserved sites of VP1 and VP4 have been used as immunogens and some evidence of cross-protection has been found. Research in these areas is ongoing to improve the efficacy and response to these vaccinations.
Another approach that is being tested is a multivalent vaccine- packing multiple serotypes into a single vaccination. In 2016, Martin Moore’s group published a study showing that a 25 valent vaccine and 50 valent vaccine in rhesus macaques was capable of inducing the production of neutralizing antibodies to RV. Their next step is to produce and test an 83-100 valent vaccine, and they hope to be in human trials within a few years.
In all, RV is a difficult target to vaccinate against due to the vast number of distinct serotypes. However, substantial progress has been made to develop vaccines through using conserved immunogens or loading vaccines with multiple serotypes. Hopefully within the near future we could see these vaccinations become available and we could deal with a few less sicknesses!
Of course, check out these references:
1. Stobart CC, Nosek JM, Moore ML. Rhinovirus Biology, Antigenic Diversity, and Advancements in the Design of a Human Rhinovirus Vaccine. Front Microbiol. 2017;8: 2412. doi:10.3389/fmicb.2017.02412
2. McLean GR. Developing a vaccine for human rhinoviruses. J vaccines Immun. 2014;2: 16–20. doi:10.14312/2053-1273.2014-3
3. Glanville N, Johnston SL. Challenges in developing a cross-serotype rhinovirus vaccine. Curr Opin Virol. 2015;11: 83–88. doi:10.1016/j.coviro.2015.03.004
4. Bochkov YA, Watters K, Ashraf S, Griggs TF, Devries MK, Jackson DJ, et al. Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication. Proc Natl Acad Sci U S A. 2015;112: 5485–5490. doi:10.1073/pnas.1421178112
5. Panjwani A, Asfor AS, Tuthill TJ. The conserved N-terminus of human rhinovirus capsid protein VP4 contains membrane pore-forming activity and is a target for neutralizing antibodies. J Gen Virol. 2016;97: 3238–3242. doi:10.1099/jgv.0.000629
6. McLean GR, Walton RP, Shetty S, Peel TJ, Paktiawal N, Kebadze T, et al. Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1. Antiviral Res. 2012;95: 193–201. doi:10.1016/j.antiviral.2012.06.006
7. Edlmayr J, Niespodziana K, Popow-Kraupp T, Krzyzanek V, Focke-Tejkl M, Blaas D, et al. Antibodies induced with recombinant VP1 from human rhinovirus exhibit cross-neutralisation. Eur Respir J. 2011;37: 44–52. doi:10.1183/09031936.00149109
8. Doggett JE, Bynoe ML, Tyrrell DAJ. Some Attempts to Produce an Experimental Vaccine with Rhinoviruses. Br Med J. 1963;1: 34 LP – 36. doi:10.1136/bmj.1.5322.34
9. Lee S, Nguyen MT, Currier MG, Jenkins JB, Strobert EA, Kajon AE, et al. A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques. Nat Commun. 2016;7: 12838. doi:10.1038/ncomms12838