The quest for a vaccine against rhinoviruses may have seemed quixotic, because there are more than 100 varieties circulating around the world. Even so, the immune system can handle the challenge, researchers from Emory University School of Medicine and Children’s Healthcare of Atlanta say.
Vaccines that combine dozens of varieties of rhinovirus at once are effective in stimulating antiviral antibodies in mice and monkeys, the researchers report in Nature Communications. The paper was also posted on Biorxiv before publication.
“We think that creating a vaccine for the common cold can be reduced to technical challenges related to manufacturing,” says Martin Moore, PhD, associate professor of pediatrics at Emory University School of Medicine.
Rhinoviruses are the most common cause of the common cold; other viruses such as respiratory syncytial virus, parainfluenza virus and adenoviruses can cause them too. Rhinoviruses also exacerbate asthma attacks. Although they come in many varieties, rhinoviruses do not drift to the same degree that influenza viruses do, Moore says.
Researchers showed in the 1960s that it was possible to vaccinate people against one variety of rhinovirus and prevent them from getting sick when challenged with samples of the same virus. The trouble was the sheer diversity of rhinoviruses – or that’s how it appeared at the time.
“It’s surprising that nobody tried such a simple solution over the last 50 years. We just took 50 types of rhinovirus and mixed them together into our vaccine, and made sure we had enough of each one,” Moore says. “If we make a vaccine with 50 or 100 variants, it’s the same amount of total protein in a single dose of vaccine. The variants are like a bunch of slightly different Christmas ornaments, not really like 50 totally different vaccines mixed.”
A mixture of 25 types of inactivated rhinovirus can stimulate neutralizing antibodies against all 25 in mice, and a mixture of 50 types can do the same thing in rhesus macaques. In this paper, antibodies generated in response to the vaccine were tested for their ability to prevent the virus from infecting human cells in culture. However, the vaccines were not tested for their ability to stop animals from getting sick.
“There are no good animal models of rhinovirus replication,” Moore says. “The next step would be human challenge models with volunteers, which are feasible because the virus is not very pathogenic.”
Emory has optioned the vaccine technology to a startup company, Meissa Vaccines, Inc., which is pursuing a product development plan with support from the National Institute of Allergy and Infectious Diseases’ vaccine manufacturing services.
In future studies, they hope to produce a comprehensive 83-valent (83 types of cold virus) HRV A vaccine. A limitation of their current study is that they have not included HRV C antigens, which will be important for HRV vaccine development, especially for paediatric populations.
As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types.
SOURCES – Emory University, Nature Communications