Final Activity Report Summary - NASAL VACCINES (Development of nasal vaccines for porcine respiratory pathogens) Intranasal vaccines (IN) offer the advantage over intramuscular or intradermal vaccines of directly targeting the immune system at the respiratory tract. Thus, in the past years there has been an effort to develop vaccines administered through this route to protect against respiratory infectious diseases. The rationale for this approach is that IN vaccines afford protective immunity at the site where the infection occurs. The main objective of this proposal was to evaluate the immune response induced by a vaccine given through the intranasal route against the Porcine Respiratory and Reproductive Syndrome Virus (PRRSV). This virus that infects young pigs causes significant economic losses and has become endemic in all countries involved in swine production including those of the European Union. To achieve our objective we have compared the immune response induced by the same vaccine injected intramuscularly or intranasally. This vaccine, which consisted of a live attenuated PRRSV, is commercially available and of common use by swine producers. In addition to the vaccinated groups, we induced the disease to a group of pigs that received the same strain of virus used for the vaccine without attenuation and used these animals as positive controls. We chose this vaccine treatment because one of the major challenges of intranasal vaccination is the delivery of sufficient antigen into the respiratory tract. Thus the use of a live attenuated vaccine would result in some degree of virus replication and in the generation of enough viral antigen to stimulate the immune system. As a result of this work we have found that only the vaccine that was given intramuscularly was able to stimulate a systemic cellular immune response. This response is of relevance to limit viral spread and persistent viral infection, which is a characteristic feature of this disease. In contrast both the infection and the vaccination through the IN route failed to induce a detectable systemic cellular immune response. In fact it has been demonstrated by others that one of the mechanisms by which PRRSV acts is by preventing the development of a fast and efficient systemic cellular response. Thus in this case, the immune response induced by nasal vaccination resembled more the infection. In addition we have found that although both vaccines induced similar levels of antibodies against the virus in serum, at the respiratory tract they failed to induce virus-specific IgA, which is one of the main mechanisms of protection against respiratory infections. However, infected animals were able to produce anti-PRRSV specific IgA at the respiratory tract. The results from our study suggest that intranasal vaccination against PRRSV with a modified live virus does not offer any advantage over the classically used intramuscular route since it delays the systemic cellular response and does not provide protective immunity at the respiratory tract (i.e. IgA). However, intramuscular vaccination also failed to induce local IgA and this might explain the fact that these vaccines only provide partial protection. Thus the design of more efficient vaccines against PRRSV should take into account the induction of local IgA and the use of combined systemic and locally administered vaccines.
