Below are a couple of figures introducing Bovine Respiratory Syncytial Virus (BRSV) and BRSV vaccines. Please refer to my doctoral thesis for a more comprehensive introduction.

Bovine Respiratory Syncytial Virus, or BRSV, is a major cause of respiratory disease in cattle worldwide, particularly in young calves, with great impact on production and animal welfare. Clinical signs range from those of a mild infection in the upper airways, to severe bronchiolitis and pneumonia. BRSV is closely related to the human RS-virus, which cause similar disease in small children.


Both BRSV and HRSV are Paramyxoviruses in the genus Pneumovirus, and both are enveloped, single strand, negative sense RNA viruses with 10 genes coding for 11 proteins, as indicated in this slide.


Protective acquired immunity against RSV depends on both antibodies and cytotoxic T-cells, which in turn turn depend on a balanced CD4 T helper cell response, as illustrated in this figure. A Th1 type response is associated with cytotoxic T-cell activity, and Th2 with a humoral response. Vaccines should induce both.


BRSV neutralizing antibodies, both in serum and in secretions, are induced by the surface proteins F and G, but other proteins, such as N and SH, induce non-neutralizing antibodies, which may have other protective properties. Cytotoxic T cell activity is induced by N, P, M2-1, F and G. As BRSV is highly prevalent, many calves receive antibodies in colostrum, referred to as maternally derived antibodies, or MDA. These MDA are partially protective against BRSV-infection, but also have a suppressive effect on the induction of humoral immune responses to immunization.


One of the major shortcomings of the several commercially available classic full-virus vaccines, both live and inactivated, is that they are unable to overcome the suppressive effect of specific MDA and induce long lasting protective immunity in young immunologically immature calves, and that they require repeated boost to protect calves during the first year of life. For these reasons, there is a need for new vaccines, with improved efficacy in young calves with MDA… New vaccines which, in addition to preventing clinical signs, can stop virus replication and thereby stop transmission of the virus. The new generation of vaccines described in my thesis use recombinant viruses or purified BRSV proteins or individually produced recombinant proteins in conjunction with novel immunostimulating adjuvants to direct and boost immune responses. The goal is to better overcome the suppressive effect of MDA in young calves and to quickly induce balanced immune responses and long lasing protective and sterilizing immunity, without repeated boost.


In addition to the drawbacks mentioned in the previous slide, classic full-virus vaccines make us serologically blind, by inducing an antibody-response identical to that seen following infection. On the other hand, new generation vaccines only induce antibodies against included proteins, and we should be able to verify this by serological analysis. But, if animals become infected and replicate virus, despite prior vaccination, we should also be able to identify these animals or herds. This is referred to as DIVA, differentiation of infected from vaccinated animals. If new vaccines are DIVA-compliant, DIVA can be used as a tool to create BRSV-free herds, to protect vaccinated animals and herds, with maintained ability to serologically monitor for circulating BRSV, but also to detect any changes in vaccine safety and efficacy.