Rhinovirus infections and immunisation induce cross-serotype reactive antibodies to VP1

Challenges in developing a cross-serotype rhinovirus vaccine

“…Intramuscular live RV immunisation in a cotton rat model caused reduced virus titres upon subsequent homologous, but not heterologous HRV infection [10]. Limited neutralising antibody crossreactivity also required multiple adjuvanted immunisations plus infection in mice [30]. That high antigenic diversity should be a barrier to vaccine design is perhaps 84 Preventive and therapeutic vaccines (B Cell Epitope Vaccine) not surprising when one considers that those neutralising epitopes described [31,32] map to VP1, VP2 and VP3 capsid protein regions that recent full length HRV genome analyses have found to be the most highly variable (as indicated by the major troughs in Figure 1) [21,33 ].…”

Understanding the Association of Human Rhinovirus with Asthma

“…Unfortunately, there are over 150 RV subtypes (66), and little cross-protection is afforded among subtypes after infection (67). The amino acid sequences of antigenic sites expressed on VP1 and other surface proteins have high intraspecies variability, but vaccination of mice with either VP2 plus VP4 antigens and adjuvant or VP1 antigens and adjuvant has produced cross-species neutralizing IgG antibodies (68,69). It is known that high homotypic antibody levels reduce symptoms on reexposure to a previously experienced strain (70), but it has been very difficult to generate cross-reactive neutralizing antibodies in humans up to this point.…”

The Application of Prophylactic Antibodies for Rhinovirus Infections

“…The recent development of a small animal model of RV infection [49] has improved investigations into potential RV therapeutic interventions and recently we have characterized the Ab responses in mice infected with RV and shown strong IgG responses to VP1 and that cross-serotype in vitro virus neutralization was generated [11]. Compared to studies in humans, this immunologically-naive model allows for simpler analyses of Ab responses without interference from Abs produced from previous encounters with RVs and may simplify the identification of novel potential prophylactic monoclonal Abs to RV through the use of mice transgenic for human immunoglobulin genes [50].…”

“…Recent studies have revealed that immunization of rabbits with recombinant VP1 generates antisera with broad cross-serotype neutralizing properties [13] and VP1 is the dominant target of Abs in both humans [12] and mice [11] following RV infection. VP1 is the central and most external of the RV capsid proteins, contains receptor binding sites for both the major and minor group RV [40], and has a high degree of amino acid identity within both type A and B RV serotypes [41,42].…”

“…Nevertheless, several Abs (approximately 10 of 200) are undergoing preclinical development or are in clinical trials for viral infectious diseases targets including HIV-1, HBV, human rhinoviruses (RV) and human cytomegalovirus [3]. RV may be particularly suited to the application of prophylactic Abs as no appropriate antiviral therapies are available despite numerous attempts [5][6][7], vaccine development faces challenging obstacles [8,9] and new information regarding protective antibody responses is being unearthed [10][11][12][13][14]. Thus, a full evaluation of the application of prophylactic Abs to these important human pathogens where there is an explicit need for appropriate therapeutic/ prophylactic interventions is warranted.…”