Preceding anti-spike IgG levels predicted risk and severity of COVID-19 during the Omicron-dominant wave in Santa Fe city, Argentina.

The SARS-CoV-2 Omicron variant has increased infectivity and immune escape compared with previous variants, and caused the surge of massive COVID-19 waves globally. Despite a vast majority (~90%) of the population of Santa Fe city, Argentina had been vaccinated and/or had been infected by SARS-CoV-2 when Omicron emerged, the epidemic wave that followed its arrival was by far the largest one experienced in the city. A serosurvey conducted prior to the arrival of Omicron allowed to assess the acquired humoral defences preceding the wave and to conduct a longitudinal study to provide individual-level real-world data linking antibody levels and protection against COVID-19 during the wave. A very large proportion of 1455 sampled individuals had immunological memory against COVID-19 at the arrival of Omicron (almost 90%), and about half (48.9%) had high anti-spike immunoglobulin G levels (>200 UI/ml). However, the antibody titres varied greatly among the participants, and such variability depended mainly on the vaccine platform received, on having had COVID-19 previously and on the number of days elapsed since last antigen exposure (vaccine shot or natural infection). A follow-up of 514 participants provided real-world evidence of antibody-mediated protection against COVID-19 during a period of high risk of exposure to an immune-escaping highly transmissible variant. Pre-wave antibody titres were strongly negatively associated with COVID-19 incidence and severity of symptoms during the wave. Also, receiving a vaccine shot during the follow-up period reduced the COVID-19 risk drastically (15-fold). These results highlight the importance of maintaining high defences through vaccination at times of high risk of exposure to immune-escaping variants.

Chronic exposure to environmental stressors enhances production of natural and specific antibodies in rats.

Although the immunosuppressive effect of chronic stress has been established, a stress response that downregulates the whole immune system does not make biological sense, especially if an animal has to endure difficult times in which there is also increased infection risk. At high animal densities, animals are faced simultaneously with food restriction (FR), social conflict (SC), and greater parasite-pathogen exposure. We hypothesized that the stress response to chronic stressors that covary with infection risk is not entirely immunosuppressive. Our prediction was that a chronically stressed animal would respond by enhancing innate defenses, while reducing investment in acquired immunity. In a laboratory setting, rats were exposed to prolonged FR and/or SC, and natural and specific antibody levels were repeatedly measured. Our prediction was fulfilled only partly, as FR and SC interacted to enhance natural antibodies, but rats exposed to either or both stressors also showed significantly higher levels of specific antibodies. These results suggest that, in the rat, chronic stress results in a prioritization of both innate and acquired humoral defenses, which makes biological sense provided the stressors examined usually signal an increased infection risk.

Trans-sialidase overcomes many antigens to be used as a vaccine candidate against Trypanosoma cruzi.

AIM: The development of vaccines against Trypanosoma cruzi remains in an exploratory stage. Despite several antigen candidates have been evaluated, a comparison among the performance of the immunogens cannot be carried out because the available reports differ in formulations and infection model. In this work, we compared the protective capacity of seven T. cruzi antigens in the same model of five new antigens and two well-established candidates. Materials & methods: We evaluated highly immunogenic proteins that contain tandem repeats (FRA [flagelar repetitive protein], Tc3, Tc6); enzymes involved in metabolic pathways critical for parasite survival (cytosolic tryparedoxin peroxidase and tryparedoxin peroxidase); and enzymes involved in parasite invasion (trans-sialidase [TS] and cruzipain). All these antigens were formulated with Freund's adjuvant and protection against the parasite infection was assessed in BALB/c mice. RESULTS: Tc3, cytosolic tryparedoxin peroxidase, cruzipain and TS showed the best outcome after infection in survival level and parasitemia. According to these data, these groups were also assessed using the ISCOMATRIX™ adjuvant which is being used in clinical trials. CONCLUSION: Taken together, our results showed that the TS overcomes the performance of other antigens when the same model is employed, confirming that TS is a promising antigen that could be used as a vaccine against T. cruzi.

Ecology of the interaction between Ixodes loricatus (Acari: Ixodidae) and Akodon azarae (Rodentia: Criceridae).

The present study explores associations of different factors (i.e. host parameters, presence of other ectoparasites and [mainly biotic] environmental factors) with burdens of Ixodes loricatus immature stages in one of its main hosts in Argentina, the rodent Akodon azarae. For 2 years, rodents were trapped and sampled monthly at 16 points located in four different sites in the Parana River Delta region. Data were analysed with generalized linear mixed models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were (a) environmental: trapping year, presence of cattle, type of vegetation, rodent abundance; (b) host parameters: body length, sex, body condition, blood cell counts, natural antibody titers and (c) co-infestation with other ectoparasites. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Most of the associations investigated were found significant, but in general, the direction and magnitude of the associations were context-dependent. An exception was the presence of cattle, which was consistently negatively associated with both larvae and nymphs independently of all other variables considered and had the strongest effect on tick burdens. Mites, fleas and Amblyomma triste were also significantly associated (mostly positively) with larval and nymph burdens, and in many cases, they influenced associations with environmental or host factors. Our findings strongly support that raising cattle may have a substantial impact on the dynamics of I. loricatus and that interactions within the ectoparasite community may be an important-but generally ignored-driver of tick dynamics.

Factors affecting patterns of Amblyomma triste (Acari: Ixodidae) parasitism in a rodent host.

Here we offer a multivariable analysis that explores associations of different factors (i.e., environmental, host parameters, presence of other ectoparasites) with the interaction of Amblyomma triste immature stages and one of its main hosts in Argentina, the rodent Akodon azarae. Monthly and for two years, we captured and sampled rodents at 16 points located at 4 different sites in the Parana River Delta region. The analyses were conducted with Generalized Linear Mixed Models with a negative binomial response (counts of larvae or nymphs). The independent variables assessed were: (a) environmental: trapping year, season, presence of cattle; type of vegetation (natural grassland or implanted forest); rodent abundance; (b) host parameters: body length; sex; body condition; blood cell counts; natural antibody titres; and (c) co-infestation with other ectoparasites: other stage of A. triste; Ixodes loricatus; lice; mites; and fleas. Two-way interaction terms deemed a priori as relevant were also included in the analysis. Larvae were affected by all environmental variables assessed and by the presence of other ectoparasites (lice, fleas and other tick species). Host factors significantly associated with larval count were sex and levels of natural antibodies. Nymphs were associated with season, presence of cattle, body condition, body length and with burdens of I. loricatus. In most cases, the direction and magnitude of the associations were context-dependent (many interaction terms were significant). The findings of greater significance and implications of our study are two. Firstly, as burdens of A. triste larvae and nymphs were greater where cattle were present, and larval tick burdens were higher in implanted forests, silvopastoral practices developing in the region may affect the population dynamics of A. triste, and consequently the eco-epidemiology of Rickettsia parkeri. Secondly, strong associations and numerous interactions with other ectoparasites suggest that co-infestations may be more important for tick dynamics than has so far been appreciated.

Differences in natural antibody titres comparing free-ranging guanacos (Lama guanicoe) and capybaras (Hydrochoerus hydrochaeris).

Natural antibodies are an important component of innate humoral immunity but have not been investigated to any great extent in wild mammals. In the current study, serum natural antibody titres were measured by hemagglutination assay for two South American herbivores, the guanaco (Lama guanicoe) and the capybara (Hydrochoerus hydrochaeris). Results indicated that capybaras had antibody titres on average more than four times higher than guanacos (median titres 1:256 and 1:4, respectively), suggesting differences in investment in constitutive humoral immunity between the two species.

Parasitism and physiological trade-offs in stressed capybaras.

Parasites play a key role in regulating wildlife population dynamics, but their impact on the host appears to be context-dependent. Evidence indicates that a synergistic interaction between stress, host condition and parasites is implicated in this phenomenon, but more studies are needed to better understand this context-dependency. With the goal to assess the net effect of two types of chronic stress on various host-parasite interactions, we conducted an experiment in capybaras to evaluate the impact of food restriction and physical restraint on the infection intensity of specific gastrointestinal nematodes and coccidia, and how these stressors affected the growth, body condition, and some immuno-physiological parameters. Our hypothesis was that both forms of stress would result in an alteration in the host-parasite interactions, with deteriorated condition and reduced immunological investment leading to high parasite burdens and vice versa. Stressed capybaras had significantly higher coccidia infection intensities; but among individuals that were smaller, those stressed consistently showed lower helminth burdens than controls. Both stress treatments had a marked negative impact on growth and body condition, but concomitantly they had a significant positive effect on some components of the immune system. Our results suggest, on the one hand, that during prolonged periods of stress capybaras preventatively invest in some components of their immunity, such as innate humoural defenses and cells that combat helminths, which could be considered a stress-dependent prophylaxis. On the other hand, stress was found to cause greater infection intensities of protozoans but lower burdens of nematodes, indicating that the relationship between stress, physiological trade-offs and infection depends on the type of parasite in question. Moreover, both findings might be related in a causal way, as one of the immunological parameters enhanced in stressed capybaras is associated with the immune response to control helminths.

Genotyping of Trypanosoma cruzi sublineage in human samples from a North-East Argentina area by hybridization with DNA probes and specific polymerase chain reaction (PCR).

We have evaluated blood samples of chronic and congenital Trypanosoma cruzi-infected patients from the city of Reconquista located in the northeast of Argentina where no information was previously obtained about the genotype of infecting parasites. Fourteen samples of congenital and 19 chronical patients were analyzed by hybridization with DNA probes of minicircle hypervariable regions (mHVR). In congenital patients, 50% had single infections with TcIId, 7% single infections with TcIIe, 29% mixed infections with TcIId/e, and 7% had mixed infections with TcIId/b and 7% TcIId/b, respectively. In Chronical patients, 52% had single infections with TcIId, 11% single infections with TcIIe, 26% had mixed infections with TcIId/e, and 11% had non-identified genotypes. With these samples, we evaluated the minicircle lineage-specific polymerase chain reaction assay (MLS-PCR), which involves a nested PCR to HVR minicircle sequences and we found a correlation with hybridization probes of 96.4% for TcIId and 54.8% for TcIIe.

Expression of HLA-G and MICA mRNA in renal allograft.

HLA-G is a nonclassical MHC class I antigen that displays tolerogenic functions; MICA is a stress-regulated molecule recognized by NKG2D cytotoxicity-activating receptor expressed by NK and T cells subsets. We evaluated HLA-G isoforms and MICA mRNA levels in peripheral blood mononuclear cells (PBMCs) and in biopsies from kidney allograft recipients with acute rejection (AR), chronic rejection (CR), and stable graft evolution (SE). HLA-G1 was the only transcript resulted from amplification, both in PBMCs as in biopsy samples. HLA-G1 mRNA levels in PBMCs from 9/10 patients with CR, 7/9 with AR and 8/10 healthy volunteers were below the median value of SE patients. The analysis of biopsies revealed that patients with AR (n=6), who overcame rejection had a tendency towards higher HLA-G1 levels than those with nephrotoxic acute tubular necrosis (ATN) (n=3). Similar levels of MICA expression were observed in PBMCs from AR, CR, SE and C groups; MICA expression levels were similar also in biopsy specimens from AR and nephrotoxic ATN patients. No correlation was found between MICA expression and the graft state. These preliminary results suggest that HLA-G1 isoforms, but not MICA mRNA levels, may provide a marker for measuring the state of kidney allograft, and be the basis for further studies that may establish the influence of these molecules in renal allograft rejection or acceptance.

Effect of two synthetic peptides mimicking conserved regions of equine infectious anemia virus proteins gp90 and gp45 upon cytokine mRNA expression.

Gp90 and gp45 synthetic peptides, which mimic conserved sequences of native viral proteins, are recognized by antibodies to equine infectious anemia virus (EIAV) in asymptomatic carrier horses and generate humoral and cellular responses in immunized mice. Cytokine mRNA levels were evaluated in equine peripheral blood mononuclear cells (PBMCs) after in vitro stimulation with gp90 and gp45 with the aim of determining the cytokine profile associated with the proliferative response. Stimulation index (SI) values indicate that 100 and 60% of EIAV-infected horses recognized gp90 and gp45, respectively. A strong positive correlation was found between IL-12p40 and SI, IFN-gamma and SI, and IL-12p40 and IFN-gamma (p < 0.001). These results suggest the presence of specific memory cells that would contribute to maintain reinfection resistance and that conserved viral regions represented by gp90 and gp45 synthetic peptides may be good candidates for inclusion in vaccine strategies against EIAV.

Effects of isomeric fatty acids on reproductive parameters in mice.

PROBLEM: The aim of this study was to determine if dietary fatty acids (FA) level or isomeric FA type may affect reproductive parameters in mice. METHOD: of study Mice were fed for 1 month diets differing in cisFA (cFA) content or type of isomeric FA. Resorption, number of fetuses and placental cytokine expression were determined and sperm acrosome reaction was evaluated after induction by calcium ionophore. RESULTS: Mice fed high fat diets showed increased fetal resorptions, a decrease in interleukin (IL)-4 placental expression in the first generation and an increase of tumor necrosis factor-alpha (TNF-alpha) in the second generation. In this generation, conjugated linoleic acid (CLA) returned TNF-alpha to normal levels and diminished IL-4 and transforming growth factor-beta (TGF-beta) expressions; males fed transFA (tFA) and CLA showed a lower rate of induced acrosome reaction. CONCLUSION: The amount and type of dietary FA may affect reproductive performance in mice by affecting sperm membrane functionality and placental cytokine production.