Role of zika virus envelope protein domain iii as a target of human neutralizing antibodies

Zika virus (ZIKV) is a flavivirus that is structurally highly similar to the related viruses, dengue virus (DENV), West Nile virus, and yellow fever virus. ZIKV causes an acute infection that often results in mild symptoms but that can cause severe disease in rare instances. Following infection, individuals mount an adaptive immune response, composed of antibodies (Abs) that target the envelope (E) glycoprotein of ZIKV, which covers the surface of the virus. Groups have studied monoclonal antibodies and polyclonal immune sera isolated from individuals who recovered from natural ZIKV infections. Some of these antibodies bind to domain III of E (EDIII), but the functional importance of these antibodies is unknown. In this study, we aimed to determine if EDIII is a major target of the potent serum neutralizing antibodies present in people after ZIKV infection. By generating a chimeric virus containing ZIKV EDIII in a DENV4 virus backbone, our data show a minor role of EDIIItargeting antibodies in human polyclonal neutralization. These results reveal that while monoclonal antibody (MAb) studies are informative in identifying individual antibody epitopes, they can overestimate the importance of epitopes contained within EDIII as targets of serum neutralizing antibodies. Additionally, these results argue that the major target of human ZIKV neutralizing antibodies resides elsewhere in E; however, further studies are needed to assess the epitope specificity of the neutralizing response at the population level. Identification of the major epitopes on the envelope of ZIKV recognized by serum neutralizing antibodies is critical for understanding protective immunity following natural infection and for guiding the design and evaluation of vaccines. IMPORTANCE Zika virus is a flavivirus that was recently introduced to Latin America, where it caused a massive epidemic. Individuals infected with ZIKV generate an immune response composed of antibodies which bind to the envelope (E) protein. These anti-E antibodies are critical in protecting individuals from subsequent infection. Multiple groups have found that many ZIKV antibodies bind to domain III of E (EDIII), suggesting that this region is an important target of neutralizing antibodies. Here, we generated a chimeric virus containing ZIKV EDIII in a dengue virus backbone to measure ZIKV EDIIIspecific antibody responses. We found that while polyclonal ZIKV immune serum contains antibodies targeting EDIII, they constitute only a small fraction of the total population of antibodies that neutralize ZIKV. Further studies are needed to define the main targets on the viral envelope recognized by human neutralizing antibodies, which is critical for guiding the development of ZIKV vaccines

Risk factors for interdigital dermatitis and heel erosion in dairy cows kept in cubicle houses in The Netherlands

Risk factors concerning both the pasture and housing seasons for interdigital dermatitis and heel-horn erosion (IDHE) were studied in dairy cows in a cross-sectional study in The Netherlands. The study population included 2326 cows (41 herds) and 2751 cows (46 herds) for the pasture and housing seasons, respectively. Of these animals, 545 (23%) showed serious lesions of IDHE (stages 2 and 3) at the end of the pasture season and 1269 (46%) during housing. Logistic regression of the pasture study indicated that increased parity, solid concrete floor, restricted grazing time, and herd trimming at long intervals were associated with an increased odds of IDHE, while dry cows and lactating cows within 30 days after calving as well as cows on a slatted floor with manure scraper, and grassland with mixed type of soil were associated with lower odds. In the housing study, odds of IDHE increased with parity, administering low- or medium-energy roughage, and introduction of dry cows into the lactating herd at >2 weeks before calving. The presence of long cubicles, knee-bumpers installed in cubicles as well as rearing calves and heifers within the dairy cows¿ accommodation decreased the odds of IDHE

Prevalence of claw disorders in Dutch dairy cows exposed to several floor systems

Claw health was examined in an observational study on Dutch dairy farms with either a slatted floor (SL), slatted floor with manure scraper (SL-SCR), solid concrete floor (SCF), a straw yard (SY), or a zero-grazing feeding system (ZG). Hooves of cows' hind legs were examined for the presence and severity of claw disorders during hoof trimming events at the end of the pasture (P-study) and housing period (H-study). The number of cows in each study was 3078 (49 herds) and 3190 (47 herds), respectively. Due to a different hoof trimming strategy, data collected during both observation periods in SY herds (638 cows; 16 herds) were combined. Cows in straw yards (SY) had by far the lowest numbers of claw disorders. Over 80% of cows exposed to concrete flooring had at least one claw disorder at the time of observation, whereas on SY surfaces, this percentage was between 55 and 60. Cows on SL-SCR were less frequently affected by interdigital dermatitis/heel erosion (IDHE) and digital dermatitis (DD) than cows on SL (reference floor system). Little difference in claw health was found between SF and SL. The ZG cows were at higher risk (OR > 2) for most claw disorders in the P-study, whereas in the H-study, ZG cows showed less IDHE, sole hemorrhage, and sole ulcer. All herds on concrete flooring (SL, SL-SCR, SCF, ZG) were infected by DD, resulting in an average cow level prevalence of 30%. This indicates that the level of DD infection has increased considerably over the last 10 yr in The Netherlands

Risk factors for digital dermatitis in dairy cows kept in cubicle houses in The Netherlands

The presence of digital dermatitis (DD) in dairy cows has increased considerably over the last 10 years in The Netherlands, resulting in a current prevalence of 30% in cows kept in cubicle houses. Our objective was to evaluate a diversified sample of cow- and herd-related risk factors for DD in dairy cows housed in cubicle houses with different flooring systems. Associations were analysed in random-effects logistic-regression models using 2134 cows (37 herds) and 2892 cows (47 herds) in the pasture and housing studies, respectively. At cow-level, the odds of having DD were increased in the case of lower parity and lactation. Important risk factors at herd-level were: restricted grazing time, fast rise in concentrate amount after calving, feeding by-products, herd trimming only at long intervals, and introduction of dry cows into the lactating herd before calving. The odds for DD were lower if cows were housed on a slatted floor with manure scraper and provided long and wide cubicles, and if calves were reared in the dairy cows¿ accommodation

Development of Claw Traits and Claw Lesions in Dairy Cows kept on different floor systems

Several claw shape measurements, horn hardness, and horn growth and wear were recorded monthly at 12 dairy farms to investigate the effect of floor type and changes in these traits over time. Herds were either housed on a slatted floor (SL), solid concrete floor (SC), grooved floor (GR), or on a straw yard (SY). Twenty cows per farm were selected and stratified by parity. Information on claw traits was recorded on right lateral hind claws between October 2002 and May 2003. In addition, lesion development of interdigital dermatitis and heel erosion (IDHE) and digital dermatitis (DD) was studied in both rear feet. No differences in claw traits were detected among groups on different floor types, with the exception of claw angle. Claw angles were smallest in cows on SY. Claws of cows on SC were steeper than those on SL and GR. The study provided no evidence that floor-related differences in claw lesions were related to differences in horn growth, wear, and resulting claw shape. Lesions of IDHE developed gradually over time and did not differ among flooring types. Cows in SY had the smallest lesion scores for DD, whereas cows on SL had significantly less DD than cows on SC and GR. Incidence of DD fluctuated over time. Development of different stages of DD was monitored in-depth. Both early and healed stages were rather changeable and often turned into other disease stages. Classical ulcerative lesions (stage M2) persisted for a long time, with 20% of the initially unaffected claws having active lesions of DD within 5 mo. The M2 lesions generally did not cure effectively after claw trimming, and frequent use of footbaths resulted in a poor prognosis for recovery

Frictional Forces Required for unrestrained locomotion in dairy cattle

Most free-stall housing systems in the Netherlands are equipped with slatted or solid concrete floors with manure scrapers. A slipping incident occurs when the required coefficient of friction (RCOF) exceeds the coefficient of friction (COF) at the claw–floor interface. An experiment was conducted to measure ground reaction forces (GRF) of dairy cows (n = 9) performing various locomotory behaviors on a nonslippery rubber-covered concrete floor. The RCOF was determined as the ratio of the horizontal and vertical components of the GRF. It was shown that during straight walking and walking-a-curve, the RCOF reached values up to the COF, whereas for sudden stop-and-start responses, the RCOF reached values beyond the maximum COF that concrete floors can provide. Our results indicate that concrete floors do not provide enough friction to allow natural locomotory behavior and suggest that tractional properties of floors should be main design criteria in the development of better flooring surfaces for cattle