Human rhinovirus (RV) is the leading cause of human infectious disease. RV contributes to exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Years ago, inactivated RV was established as a protective vaccine, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of over 150 discouraged vaccine development. We hypothesize that a highly polyvalent RV vaccine is feasible with sufficiently high antigen load per RV type.
Polyvalent vaccines consisted of high-titer RVs. Rhinoviruses were inactivated with formalin, mixed with alum adjuvant, and administered by intramuscular injection in a prime and boost regimen. BALB/c mice were vaccinated with 1, 3, 5, 7, 10, or 25-valent RV vaccine. Rhesus macaques were vaccinated with 25-valent or 50-valent RV. Immunogenicity of these vaccines was measured by in vitro virus nAb assays against each RV type.
In mice, we observed that antisera neutralized 100% of RV types in the 10-valent vaccine and 96% of RV types in the 25-valent vaccine. Antisera from rhesus macaques neutralized 100% of RV types in the 25-valent and 98% of RV types in the 50-valent vaccine. RV vaccine immunogenicity correlated with the quantity of input antigens, and valency was not a major determinant for potency or breadth of the immunogenicity.
This is the first study showing a polyvalent inactivated RV vaccine capable of inducing broad nAb responses to numerous and diverse RV types. The approach demonstrated here provides proof of principle for the feasibility of a polyvalent rhinovirus vaccine approach that could alleviate RV-induced asthma exacerbation.