Application of the Nagoya Protocol to veterinary pathogens: concerns for the control of foot-and-mouth disease

The Nagoya Protocol is an international agreement adopted in 2010 (and entered into force in 2014) which governs access to genetic resources and the fair and equitable sharing of benefits from their utilisation. The agreement aims to prevent misappropriation of genetic resources and, through benefit sharing, create incentives for the conservation and sustainable use of biological diversity. While the equitable sharing of the benefits arising from the utilisation of genetic resources is a widely accepted concept, the way in which the provisions of the Nagoya Protocol are currently being implemented through national access and benefit-sharing legislation places significant logistical challenges on the control of transboundary livestock diseases such as foot-and-mouth disease (FMD). Delays to access FMD virus isolates from the field disrupt the production of new FMD vaccines and other tailored tools for research, surveillance and outbreak control. These concerns were raised within the FMD Reference Laboratory Network and were explored at a recent multistakeholder meeting hosted by the European Commission for the Control of FMD. The aim of this paper is to promote wider awareness of the Nagoya Protocol, and to highlight its impacts on the regular exchange and utilisation of biological materials collected from clinical cases which underpin FMD research activities, and work to develop new epidemiologically relevant vaccines and other diagnostic tools to control the disease

Mucosally Delivered Salmonella Live Vector Vaccines Elicit Potent Immune Responses against a Foreign Antigen in Neonatal Mice Born to Naive and Immune Mothers

The development of effective vaccines for neonates and very young infants has been impaired by their weak, short-lived, and Th-2 biased responses and by maternal antibodies that interfere with vaccine take. We investigated the ability of Salmonella enterica serovars Typhi and Typhimurium to mucosally deliver tetanus toxin fragment C (Frag C) as a model antigen in neonatal mice. We hypothesize that Salmonella, by stimulating innate immunity (contributing to adjuvant effects) and inducing Th-1 cytokines, can enhance neonatal dendritic cell maturation and T-cell activation and thereby prime humoral and cell-mediated immunity. We demonstrate for the first time that intranasal immunization of newborn mice with 10(9) CFU of S. enterica serovar Typhi CVD 908-htrA and S. enterica serovar Typhimurium SL3261 carrying plasmid pTETlpp on days 7 and 22 after birth elicits high titers of Frag C antibodies, previously found to protect against tetanus toxin challenge and similar to those observed in adult mice. Salmonella live vectors colonized and persisted primarily in nasal tissue. Mice vaccinated as neonates induced Frag C-specific mucosal and systemic immunoglobulin A (IgA)- and IgG-secreting cells, T-cell proliferative responses, and gamma interferon secretion. A mixed Th1- and Th2-type response to Frag C was established 1 week after the boost and was maintained thereafter. S. enterica serovar Typhi carrying pTETlpp induced Frag C-specific antibodies and cell-mediated immunity in the presence of high levels of maternal antibodies. This is the first report that demonstrates the effectiveness of Salmonella live vector vaccines in early life

Evaluation of serological response to foot-and-mouth disease vaccination in BLV infected cows

Bovine Leukemia Virus (BLV) produces disorders on the immune system in naturally infected animals, which may counteract the development of immunity after vaccination. The aim of this study was to investigate whether healthy and BLV infected cattle elicited similar humoral responses after foot and mouth disease (FMD) immunization. In a field study, 35 Holstein heifers were selected based on their BLV serological status and immunized with a single dose of a commercial bivalent oil-based FMD vaccine. Serum samples were collected at 0, 15, 60, 165 and 300 days post vaccination (dpv)Inst.de VirologíaFil: Puentes, Rodrigo. Universidad de la República. Facultad de Veterinaria. Area Inmunología; UruguayFil: De Brun, Laureana. Universidad de la República. Facultad de Veterinaria. Area Inmunología; UruguayFil: Algorta, Agustina. Universidad de la República. Facultad de Veterinaria. Area Inmunología; UruguayFil: Da Silva, Valeria. Universidad de la República. Facultad de Veterinaria. Area Inmunología; UruguayFil: Mansilla, Florencia Celeste. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; ArgentinaFil: Sacco, Gustavo. Práctica profesional independiente; UruguayFil: Llambí, Silvia. Universidad de la República. Facultad de Veterinaria. Area Genética; UruguayFil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Development of DNA Vaccines against Hemolytic-Uremic Syndrome in a Murine Model

Shiga toxin type 2 (Stx2) produced by Escherichia coli O:157H7 can cause hemolytic-uremic syndrome in children, a disease for which there is neither a vaccine nor an effective treatment. This toxin consists of an enzymatically active A subunit and a pentameric B subunit responsible for the toxin binding to host cells, and also found to be immunogenic in rabbits. In this study we developed eukaryotic plasmids expressing the B subunit gene of Stx2 (pStx2B) and the B subunit plus the gene coding for the A subunit with an active-site deletion (pStx2ΔA). Transfection of eukaryotic cells with these plasmids produced proteins of the expected molecular weight which reacted with specific monoclonal antibodies. Newborn and adult BALB/c mice immunized with two intramuscular injections of each plasmid, either alone or together with the same vector expressing the granulocyte and monocyte colony-stimulating factor (pGM-CSF), elicited a specific Th1-biased humoral response. The effect of pGM-CSF as an adjuvant plasmid was particularly notable in newborn mice and in pStx2B-vaccinated adult mice. Stx2-neutralizing activity, evaluated in vitro on VERO cell monolayers, correlated with in vivo protection. This is the first report using plasmids to induce a neutralizing humoral immune response against the Stx2

Systemic antibodies administered by passive immunization prevent generalization of the infection by foot-and-mouth disease virus in cattle after oronasal challenge

The role of passively transferred sera in the protection against aerogenous foot-and-mouth disease (FMD) virus infection in cattle was evaluated using vaccine-induced immune serum preparations obtained at 7 and 26 days post-vaccination (dpv). We showed that circulating antibodies were sufficient to prevent disease generalization after oronasal infection in animals passively transferred with 26-dpv serum but not with the 7-dpv serum. Conversely, conventional FMD vaccination provided clinical protection at 7 dpv, promoting fast and robust antibody responses upon challenge and even though antibody titers were similar to those found in animals passively immunized with 7-dpv serum. These results demonstrate that presence of antigen-specific antibodies is critical to prevent the dissemination of the virus within the animal. Conventional FMD vaccination additionally promoted the deployment of rapid, high titer and isotype-switched antibody responses at systemic and mucosal levels after infection, thus conferring protection even in the presence of low pre-challenge antibody titers.Fil: Barrionuevo, Florencia Mariel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Giacomo, Sebastián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Bucafusco, Danilo. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ayude, Andrea. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Schammas, Juan. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Miraglia, Maria Cruz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Capozzo, Alejandra Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; ArgentinaFil: Borca, Manuel V.. United States Department of Agriculture; Estados UnidosFil: Pérez Filgueira, Daniel Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Virología; Argentin