Papers by Alejandra Capozzo
Frontiers in Veterinary Science, Nov 6, 2023
The role of water buffaloes in foot-and-mouth disease (FMD) epidemiology as one of the major host... more The role of water buffaloes in foot-and-mouth disease (FMD) epidemiology as one of the major hosts of the virus that can develop persistent asymptomatic infection highlights the importance of sustaining surveillance on the antibody response elicited by vaccination in these animals. There is gap in the knowledge on how serological assays that measure antibodies against capsid proteins perform with buffalo samples and which would be the most reliable test to substitute the virus neutralization test (VNT) a cumbersome and low-throughput tool for field surveillance. Alternatively, the liquid-phase blocking sandwich ELISA (LPBE) is commonly used. Previous data from our laboratory demonstrated that the vaccine-induced antibodies assessed by the LPBE yielded low specificity with buffaloes' samples. In contrast, a single-dilution avidity ELISA (AE) aimed to detect high-avidity antibodies against exposed epitopes, combined with an indirect ELISA (IE) to assess IgG levels, produced more reliable results. Here we analyzed for the first time the kinetics of the antibodies induced by vaccination in two different buffalo herds (n = 91) over 120 days using AE, IE, LPBE, and the VNT. Kinetics were similar in the different assays, with an increase of antibodies between 0-and 14days post-vaccination (dpv) which were maintained thereafter. VNT and AE results were concordant (Kappa value = 0.76), and both assays revealed a decay in the antibody response in calves with maternal antibodies at 90 and 120 dpv, which was not evidenced by the LPBE. These results show that kinetics of antibody responses to FMD vaccination are similar in buffalo and cattle, and support the use of indirect ELISA assays, in particular Avidity ELISA, as alternatives to the VNT for vaccine-immunity monitoring irrespectively of the animal's passive or active immune status.
Journal of Basic and Applied Genetics
Human interferon-λ4 is a cytokine involved in early stages of antiviral responses. Strikingly, so... more Human interferon-λ4 is a cytokine involved in early stages of antiviral responses. Strikingly, some allelic variants with diminished antiviral activity reduce the susceptibility to viral infections, thus they would have suffered a positive selection pressure throughout the evolutionary history of the genus Homo. An intronic variant within the IFNλ4 locus (rs12979860, T˃C) emerged as one of the main gene determinants of the response to HCV and other viruses. The rs12979860-C allele has a differential frequency in African, European and Native American populations, though South American data are scarce. Here we characterize for the first time the distribution of rs12979860 genotypes in a sample of the global population of Buenos Aires, Argentina, assessing its association with European, Native American and African parental components. The rs12979860 genotypes were determined by PCR-RFLP in DNA samples from donors of a blood banks of Buenos Aires (n=96), whose genetic individual ancestr...
implementación de una estrategia sanitaria de control del virus de la diarrea viral bovina en un ... more implementación de una estrategia sanitaria de control del virus de la diarrea viral bovina en un establecimiento de cría ANSELMO ODEÓN; ERIKA GONZÁLEZ ALTAMIRANDA; MERCEDES GOIZUETA; ANDREA VERNA; ENRIQUE LOUGE URIARTE; MAXIMILIANO SPETTER; ERNESTO SPÄTH; ANDRÉS CASTELLANO; ERNESTO ODRIOZOLA; GERMÁN CANTÓN; JAVIER FERNÁNDEZ; JORGE FINELLI; SUSANA PEREYRA, MARÍA LEUNDA; VERÓNICA RECALT; ALEJANDRA CAPOZZO Y DARÍO MALACARI
Frontiers in Veterinary Science
Journal of virology, Jan 8, 2015
Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. C... more Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days post-vaccination (dpv), reaching a plateau until 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, though in lower numbers. Twenty-nine dpv a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animal...
Vaccine, 2019
Foot-and-mouth disease (FMD) vaccines must be carefully selected and their application closely mo... more Foot-and-mouth disease (FMD) vaccines must be carefully selected and their application closely monitored to optimise their effectiveness. This review covers serological techniques for FMD vaccine quality control, including potency testing, vaccine matching and post-vaccination monitoring. It also discusses alternative laboratory procedures, such as antigen quantification and nucleotide sequencing, and briefly compares the approaches for FMD with those for measuring protection against influenza virus, where humoral immunity is also important. Serology is widely used to predict the protection afforded by vaccines and has great practical utility but also limitations. Animals differ in their responses to vaccines and in the protective mechanisms that they develop. Antibodies have a variety of properties and tests differ in what they measure. Antibody-virus interactions may vary between virus serotypes and strains and protection may be affected by the vaccination regime and the nature and timing of field virus challenge. Finally, tests employing biological reagents are difficult to standardise, whilst cross-protection data needed for test calibration and validation are scarce. All of this is difficult to reconcile with the desire for simple and universal criteria and thresholds for evaluating vaccines and vaccination responses and means that oversimplification of test procedures and their interpretation can lead to poor predictions. A holistic approach is therefore recommended, considering multiple sources of field, experimental and laboratory data. New antibody avidity and isotype tests seem promising alternatives to evaluate crossprotective, post-vaccination serological responses, taking account of vaccine potency as well as match. After choosing appropriate serological tests or test combinations and cutoffs , results should be interpreted cautiously and in context. Since opportunities for experimental challenge studies of crossprotection are limited and the approaches incompletely reflect real life, more field studies are needed to quantify cross-protection and its correlation to in vitro measurements.
Frontiers in Veterinary Science
Viruses
Foot-and-mouth disease (FMD) remains one of the major threats to animal health worldwide. Its cau... more Foot-and-mouth disease (FMD) remains one of the major threats to animal health worldwide. Its causative agent, the FMD virus (FMDV), affects cloven-hoofed animals, including farm animals and wildlife species, inflicting severe damage to the international trade and livestock industry. FMDV antigenic variability remains one of the biggest challenges for vaccine-based control strategies. The current study analyzed the host’s adaptive immune responses in cattle immunized with different vaccine protocols and investigated its associations with the clinical outcome after infection with a heterologous strain of FMDV. The results showed that antigenic payload, multivalency, and revaccination may impact on the clinical outcome after heterologous challenge with FMDV. Protection from the experimental infection was related to qualitative traits of the elicited antibodies, such as avidity, IgG isotype composition, and specificity diversity, modulating and reflecting the vaccine-induced maturation...
Structure-based drug design for envelope protein E2 uncovers a new class of bovine viral diarrhea... more Structure-based drug design for envelope protein E2 uncovers a new class of bovine viral diarrhea inhibitors that block virus entry, Antiviral Research (2017),
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Frontiers in Veterinary Science
The Coronavirus Disease 2019 (COVID-19) is a zoonotic disease caused by the pandemic virus SARS-C... more The Coronavirus Disease 2019 (COVID-19) is a zoonotic disease caused by the pandemic virus SARS-CoV-2. Domestic and wild animals are susceptible to infection and are potential reservoirs for virus variants. To date, there is no information about the exposure of companion animals in Buenos Aires Suburbs, the area with the largest population in Argentina where the highest number of COVID-19 human cases occurred during the first infection wave. Here we developed a multi-species indirect ELISA to measure antibodies reactive to the SARS-CoV-2 receptor-binding domain (RBD) from several vertebrates constituting the class Mammalia, making it a valuable tool for field serosurveillance. The ELISA cut-off value was estimated by sera from dogs, cats, cattle, and pigs sampled before 2019 (n = 170), considering a 98% percentile and a grey zone to completely exclude any false positive result. Specificity was confirmed by measuring levels of neutralizing antibodies against canine coronavirus, the a...
Vaccine, 2017
Foot-and-mouth disease (FMD) vaccines with improved stability and less reliant on a cold-chain ar... more Foot-and-mouth disease (FMD) vaccines with improved stability and less reliant on a cold-chain are needed to improve the longevity of immune responses elicited in animals. This is especially so for serotypes O and SAT2 which are unstable in mildly acidic pH conditions or at elevated temperatures leading to dissociation of the capsid (146S particle) and loss of immunogenicity. Previously, stabilised SAT2 viruses were generated by reverse genetic approaches and assessed in vitro and in vivo with a guinea pig trial. Here we investigated the efficacy and comparative immunological responses of two thermostable and wild-type SAT2 vaccines over 5 months followed by challenge. We assessed humoral immune responses elicited in cattle in terms of total and neutralizing antibodies and IgG1/2 isotyping; and cell-mediated responses of IFN-c as in vitro markers of protection. Whilst there were significant differences in total and neutralizing antibodies for the vSAT2-93H group compared to other vaccinated groups after the first vaccination, there were no significant differences after the second immunization. Following intra-dermolingual challenge all vaccinated groups were fully protected as determined by the absence of generalized lesions. These results provide proof that two vaccine doses, consisting of SAT2 antigen combined with ISA206B adjuvant, administered 4-6 weeks apart were able to protect animals up to 5 months pv. Additionally, vSAT2-93Y had significantly higher levels of IFN-c after challenge and had a lower clinical score indicative of better protection compared to other vaccinated groups and the importance of cell mediated responses and antigen stability in protection.
Sociedad Argentina de Medicina, Dec 29, 2020
Carta al Editor.Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria. ... more Carta al Editor.Fil: Capozzo, Alejandra Victoria. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; Argentin
Journal of Dairy Science
Little is known about the influence of maternal antibodies and immune cells transferred through c... more Little is known about the influence of maternal antibodies and immune cells transferred through colostrum on the immune responses of calves to the currently used foot-and-mouth disease (FMD) vaccines. Here we evaluated the humoral and cellular immune responses induced by vaccination of colostrum-deprived calves and calves that received equivalent amounts of colostrum preparations that differed in the presence or absence of maternal immune cells but contained the same quantity and quality of anti-foot-and-mouth disease virus (FMDV) antibodies. Three groups of 32-d-old calves (n = 3 per group) were deprived of colostrum and fed either whole immune colostrum or a cell-free colostrum preparation containing only anti-FMDV antibodies. All groups were immunized with 1 dose of an oil-adjuvanted commercial vaccine. Blood samples were collected periodically before vaccination and weekly after vaccination. Immune responses specific to FMDV were assessed based on T-cell proliferation, IFN-γ production, total and neutralizing serum antibodies, and isotype profile. All vaccinated calves developed IFN-γ and lymphoproliferative responses, irrespective of the colostrum received. Colostrum-deprived animals responded to vaccination with a primary IgM response followed by an increase of IgG1 titers. Conversely, antibody titers decreased in all colostrum-fed calves after vaccination. This study demonstrates for the first time that maternal immune cells transferred to the calves through colostrum do not modify immune responses to FMD vaccine, and it confirms the interference of maternal antibodies in the induction of humoral but not cell-mediated immune responses.
Fil: Mansilla, Florencia Celeste. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Arg... more Fil: Mansilla, Florencia Celeste. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina. Instituto Nacional de Tecnologia Agropecuaria. Centro de Investigacion en Ciencias Veterinarias y Agronomicas; Argentina
Frontiers in Veterinary Science
Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The diseas... more Bovine-viral-diarrhea virus (BVDV) can cause significant economic losses in livestock. The disease is controlled with vaccination and bovines are susceptible until vaccine immunity develops and may remain vulnerable if a persistently infected animal is left on the farm; therefore, an antiviral agent that reduces virus infectivity can be a useful tool in control programs. Although many compounds with promising in-vitro efficacy have been identified, the lack of laboratory-animal models limited their potential for further clinical development. Recently, we described the activity of type I and III interferons, IFN-α and IFN-λ respectively, against several BVDV strains in-vitro. In this study, we analyzed the in-vivo efficacy of both IFNs using a BALB/c-mouse model. Mice infected with two type-2 BVDV field strains developed a viremia with different kinetics, depending on the infecting strain's virulence, that persisted for 56 days post-infection (dpi). Mice infected with the low-virulence strain elicited high systemic TNF-α levels at 2 dpi. IFNs were first applied subcutaneously 1 day before or after infection. The two IFNs reduced viremia with different kinetics, depending on whether either one was applied before or after infection. In a second experiment, we increased the number of applications of both IFNs. All the treatments reduced viremia compared to untreated mice. The application of IFN-λ pre-and post-infection reduced viremia over time. This study is the first proof of the concept of the antiviral potency of IFN-λ against BVDV in-vivo, thus encouraging further trails for a potential use of this cytokine in cattle.
Journal of Virology, 2005
Measles virus (MV) hemagglutinin (MV-H) and fusion (MV-F) proteins induce plaque reduction neutra... more Measles virus (MV) hemagglutinin (MV-H) and fusion (MV-F) proteins induce plaque reduction neutralizing (PRN) antibodies and cell-mediated immune responses that protect against clinical measles. DNA vaccines that encode MV-H and MV-F are being investigated as a new generation of measles vaccine to protect infants too young to receive currently licensed attenuated measles vaccines. However, it is unclear whether DNA vaccines encoding both MV-H and MV-F act synergistically to induce stronger immunity than immunization with plasmids encoding MV-H or MV-F alone. To address this question, we generated Sindbis virus-based pSINCP DNA vaccines that encode either MV-H or MV-F alone or bicistronic or fusion system vectors that encode both MV-H and MV-F (to mimic MV infection where both MV-H and MV-F proteins are expressed by the same mammalian cell). Mice immunized with DNA vaccine encoding MV-H alone developed significantly greater PRN titers than mice immunized with bicistronic constructs. ...
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Papers by Alejandra Capozzo