Interference of MDA with vaccination is a major concern when young piglets are to be vaccinated. The mechanisms by which that interference occurs are not fully elucidated. However, there is strong evidence favouring the hypothesis that blocking by MDA may involve the inhibition of B-cell responses by the cross-linking between B cell receptor with the Fcγ-receptor IIB by a vaccine–antibody complex, regardless of the neutralising capacity of the antibodies involved [3, 10, 11].
The intradermal administration of vaccines is an increasingly interesting alternative for vaccination, being less invasive and more respectful of animal welfare [12]. Interference with MDA could also be diminished by this vaccination route, as shown for the human poliovirus vaccine administered to children [13]. The skin has a rich diversity of antigen-presenting cells that are highly efficient for capturing and transporting antigens to the draining lymph nodes. Of special interest are Langerhans cells that are particularly able to induce cytotoxic T cells [14] but are less efficient in inducing responses from B cells. On the other hand, in humans, CD14+ dermal dendritic cells are especially able to prime naïve B cells. This diversity of antigen-presenting cells in the skin can be advantageous for achieving effective immune responses after vaccination even when reduced amounts of antigen are available. Several studies proved that reduced doses of dermally-delivered antigens are effective for immunizing children with MDA against poliovirus [13, 15].
In the case of PRRSV, the intradermal administration of MLV PRRSV vaccines has proven to be as effective as the IM administration in naïve MDA-free pigs [6–9, 16]. The vaccine tested in the present study showed that both routes were equally effective in developing immunity against PRRS in absence of MDA, which is in line with what showed by the above authors; moreover, the vaccine was demonstrated to be able to produce similar levels of immunity by means both routes even in presence of high MDA levels. It is worth mentioning here that, in PRRSV endemic farms, circulation of the virus often starts in the farrowing units because of the existence of vertical transmission from sows to newborns, or very soon after weaning since MDA wane between 4 and 5 weeks of age (reviewed by Pileri and Mateu [17]). Given the fast spread of the virus in naïve populations, vaccination of piglets must be administered at weaning or even before, implying that most vaccinated piglets will have MDA. Since the neutralising antibodies against PRRSV usually have a narrow breadth of neutralisation, the capability of MDA to neutralise a particular vaccine virus will depend on what vaccine was used in the sows and on their previous contact with other PRRSV strains.
The most remarkable results were on animals of seropositive origin, which presented a stronger humoral response despite having high levels of MDA. This was clear for both S/P values (particularly for ID-POS) and virus neutralising antibodies (NA) titres.
It is worth noting here that the scenario selected for the study was that where seropositive piglets did not have NA against the vaccine virus. Since NA in PRRS usually have a narrow range of neutralisation [18], this scenario would account for most situations, including the vaccination of the offspring of sows vaccinated with a different vaccine, or simply, of seropositive unvaccinated sows. Although NA may have a role in blocking the replication of the MLV virus, it is known that vaccine blocking by the MDA is not necessarily related to the presence of NA [3].
This phenomenon of increased response to vaccination in individuals with sub-neutralising levels of antibodies has been proven in humans that were vaccinated with an experimental attenuated vaccine against the dengue virus [19, 20]. In that case, the greater immune response in individuals with antibodies was attributed to increased infection of macrophages mediated by virus-antibody complexes. In the present case, Ct values of POS animals at 7 dpv were similar or lower to those of NEG animals. However, it is worth noting that there were more PCR-positive pigs at 7 dpv in the POS (IM and ID) compared to the NEG groups.
The design could have certainly overlooked the case of animals with high homologous NA titres. Renson et al. [1] showed that homologous neutralising MDA titres of about 1:10 may produce some interference with the development of immunity in piglets. The interference of MDA antibodies resulting from vaccination with different vaccines should be evaluated in the future.
Regarding the cell-mediated responses, the presence of MDA did not significantly interfere with the development of proliferative or IFN-γ responses. In other studies, it has been shown that vaccine blocking by MDA usually affects the development of humoral responses but not the development of cell-mediated immunity [21, 22].
In the present case, the development of vaccine-induced viremia was similar in all groups following a pattern described in other previous works [1, 23]. As shown before, some animals did not develop detectable viremia while others persisted as positive for several weeks. One possible element involved in this different behaviour could have been the IFN-α response. Renson et al. [1] reported a potential correlation of this phenomenon with decreased response to the vaccine. This was not our case since all animals had comparable levels of this cytokine in serum.
Interestingly, the results showed that seronegative animals had a higher probability of having high levels of IL-12 in serum after vaccination than seropositive ones. This suggests a differential targeting of TLRs in animals with or without antibodies against the vaccine virus. Most of the animals with the highest IL-12 levels in serum were the ones with high IL-10 levels. A possible explanation could be in the homeostatic action of IL-10 o counterbalance excessive IL-12 production. It is known that IL-10 is a potent regulator of IL-12 transcription [24].
These results raise questions concerning the role of MDA in PRRS vaccination. The present results would indicate that in cases where the MDA were subneutralising (i.e., heterologous vaccines in sows and piglets), humoral immunity induced by MLV vaccination could even be enhanced. Further research should be done in this area to figure out what were the mechanisms leading to this difference including the possible enhancement of the vaccine virus replication and also whether vaccine-antibody complexes result in different stimulation of antigen-presenting cells.