Maternally Derived Antibodies Titres Research Articles

Descriptive analyses of maternally-derived antibody levels against porcine circovirus 2 (PCV-2) in 3- and 21-day-old piglets from farms of four European countries using different vaccination protocols in sows

BackgroundUp to now, information on the levels of maternally-derived antibodies (MDA) against PCV-2 in suckling piglets born to sows vaccinated with different strategies is scarce in the literature. In the present observational study, the PCV-2-specific MDA titres from piglets from 109 farms (thirty 3-day-old and thirty 21-day-old piglets per farm) across four different European countries (France n = 30, Germany n = 27, Italy n = 22 and Spain n = 30) using different sow vaccination strategies (during gestation, as a gilt, as a piglet or never) were assessed.ResultsIn all four countries, mean log PCV-2 MDA titres were higher in 3-day-old piglets than in the 3-week-old ones, being significant in most of all the comparisons performed. Within each country, the highest PCV-2-specific MDA titres were observed in the 3-day-old piglets born to sows vaccinated during gestation. Indeed, in the four countries, more than 60% of this subpopulation (3-day-old piglets from sows vaccinated during pregnancy) had the highest log PCV-2 titres detectable with the ELISA technique used in this study. The lowest MDA titres were more variable. Whereas in France and Germany the lowest titres corresponded to 21-day-old piglets born from sows vaccinated as a piglet, in Italy, they corresponded to 21-day-old piglets derived from sows vaccinated as a gilt and in Spain to 21-day-old piglets born from non-vaccinated sows. In this study, PCV-2-specific MDA titres at 3 and 21 days of age were not affected by sow parity.ConclusionsData obtained could be considered as a European global overview of PCV-2-specific MDA titres present in the pre-vaccinated piglet populations in different European countries, with titres tending to be higher in younger piglets, but with values variable among countries and sow vaccination strategies.

Effect of maternal antibodies on the immune response to different canine parvovirus vaccines and antibody response to selected vaccines

Canine parvovirus (CPV) is the main cause of gastroenteritis and mortalities in young dogs worldwide. Despite vaccination, the outbreaks of canine parvovirus infection occur in many countries including Sri Lanka. Interference caused by maternally derived antibodies (MDA) is a main reason for vaccination failure. Present study assessed the level of CPV specific MDA in puppies prior to vaccination, the effect of MDA on the efficacy of different preparations of CPV vaccines and, evaluated the immunogenicity of selected CPV vaccines available commercially. Analysis of MDA in puppies born to vaccinated or unvaccinated mothers using commercially available point of care ELISA based test revealed the presence of protective levels of MDA titres at 8 weeks of age which can affect the immunogenicity of the vaccines containing inactivated virus or low viral titre (1000 HAU). The vaccines containing CCID 50 of ≥103-5 were able to induce antibody titres higher than protective level. Analysis of CPV-2 specific antibody titres, two weeks after completing the primary CPV vaccination (16-18 weeks of age) revealed that the dogs who received the vaccines containing CPV-2 or CPV-2b strain with >105 CCID 50 induced significantly high levels of mean antibody titre (vaccine “B”- p value = 0.004; vaccine “D” - p value = 0.022; vaccine “F”- p value = 0.032) when compared to the vaccine containing 1000 HAU. In conclusion, it was evident that the interference of MDA on CPV vaccines could be circumvented by using a live attenuated CPV vaccine having a high viral dose of CPV. Low viral dose vaccines and inactivated vaccines are not suitable for primary vaccination as those could be interfered by maternal immunity.

Immunogenicity of E2CD154 Subunit Vaccine Candidate against Classical Swine Fever in Piglets with Different Levels of Maternally Derived Antibodies.

E2CD154 is a novel subunit vaccine candidate against classical swine fever virus (CSFV). It contains the E2 envelope protein from CSFV fused to the porcine CD154 molecule formulated in the oil adjuvant MontanideTM ISA50 V2. Previous works evidenced the safety and immunogenicity of this candidate. Here, two other important parameters related to vaccine efficacy were assessed. First, the existence of high maternally derived antibody (MDA) titers in piglets born to sows vaccinated with E2CD154 was demonstrated. These MDA titers remained above 1:200 during the first seven weeks of life. To assess whether the titers interfere with active vaccination, 79 piglets from sows immunized with either E2CD154 or a modified live vaccine were vaccinated with E2CD154 following a 0–21-day biphasic schedule. Animals immunized at either 15, 21, or 33 days of age responded to vaccination by eliciting protective neutralizing antibody (NAb) titers higher than 1:600, with a geometric mean of 1:4335, one week after the booster. Those protective levels of NAb were sustained up to six months of age. No vaccination-related adverse effects were described. As a conclusion, E2CD154 is able to induce protective NAb in piglets with different MDA levels and at different days of age.

Efficacy of a live intranasal vaccine against parainfluenza type 3 and bovine respiratory syncytial virus in young calves with maternally derived antibodies

Trial designTwo randomised controlled vaccination trials with artificial challenges were carried out in addition to a serological survey of levels of maternally derived antibodies (MDA) to parainfluenza type 3 virus...

Oral administration of modified live canine parvovirus type 2b induces systemic immune response

Different strategies have been proposed to overcome maternally derived antibody (MDA) interference with canine parvovirus type 2 (CPV-2) immunisation, including intranasal vaccination, which presents some practical limitations. In the present study, the results of the oral administration of a commercial CPV-2b modified live virus (MLV) vaccine in pups with MDA are reported. The CPV-2b vaccine was orally administered to 14 6-week-old pups with a bait. Blood samples and rectal swabs were collected at different days post-vaccination (dpv) to determine CPV-2 antibody titres and DNA loads. Thirteen pups were positive to serological and virological tests after the first vaccination and one pup became positive after the second vaccine administration. The findings of this study suggest that systemic immunity against CPV-2 may be achieved by the use of an MLV CPV-2b vaccine administered orally even in the presence of MDA titres that usually interfere with vaccination.

Effect of Porcine circovirus 2 (PCV-2) maternally derived antibodies on performance and PCV-2 viremia in vaccinated piglets under field conditions

BackgroundNowadays, the most common presentation of PCV-2 is the subclinical infection in piglets after weaning. The success of PCV-2 vaccination is associated with the control of the clinical disease as well as the improvement of production parameters. In consequence, the objective of the present study was to analyse the effect of PCV-2 maternally derived antibody (MDA) levels on vaccine efficacy in piglets vaccinated at three weeks of age with a commercial PCV-2 subunit vaccine. The study was performed analysing a database with 6112 wean-to-slaughter piglets from 4 different European regions.ResultsResults showed that the use of the vaccine was able to decrease the PCV-2 viremia calculated as area under the curve (AUC = 60.29 ± 3.73), increase average daily weight gain (ADWG = 0.65 ± 0.01 kg/day) and reduce mortality (7%) in vaccinated piglets compared to non-vaccinated ones (AUC of 198.27 ± 6.14, 0.62 ± 0.01 kg/day and 11% respectively). The overall difference of ADWG between both groups was close to 30 g per day (p < 0.05), also when they were split for low and high levels of MDA titres. Moreover, the animals with the highest ADWG were observed in the group of piglets vaccinated with high or extremely high antibody titres (0.66 and 0.65 kg/day respectively). Considering only animals with extremely high antibody titres, both study groups performed similar, however there was a numerical difference of 10 g/day in favour of vaccinated piglets. Likewise, lack of correlation between ADWG and MDA was observed suggesting that no maternal antibody interference was present with the tested vaccine because the vaccinated animals grew faster compared to unvaccinated control animals, regardless of the level of maternal antibodies present at the time of vaccination.ConclusionsThe results of the present study demonstrated that the MDA against PCV-2 transferred through the colostrum intake has a protective effect against this viral infection. The vaccine used in the present study (Ingelvac CircoFLEX®) was effective when applied at three weeks of age and was not affected by the level of MDA at the time of vaccination.

Comparison of the effectiveness of rHVT-H5, inactivated H5 and rHVT-H5 with inactivated H5 prime/boost vaccination regimes in commercial broiler chickens carrying MDAs against HPAI H5N1 clade 2.2.1 virus

Vaccination is the main tool implemented in Egypt since 2007 to control H5N1 avian influenza. The present study aimed at comparing the effectiveness of three avian influenza vaccination regimes in commercial broiler chickens carrying high levels of maternally derived antibodies (MDAs). Day-old chicks were divided into four experimental groups. Group I received only the rHVT-H5 vaccine (recombinant turkey herpesvirus (HVT) which carries a H5 clade 2.2 insert) administered at D1. Group II received only the KV-H5 (an oil emulsion killed vaccine prepared from reassortant HPAI virus (A/duck/Anhui/1/06)) vaccine (inactivated reverse genetic H5N1 clade 2.3.4 virus) administered at D8. Group III received rHVT-H5 and KV-H5 as prime/boost. Group IV served as unvaccinated control. Weekly serological monitoring was conducted using the haemagglutination inhibition test. Two challenge experiments were conducted at D28 and D35 using HPAI H5N1 clade 2.2.1 virus. Birds were monitored daily 14 days post-challenge for morbidity and mortality, and oropharyngeal swabs were collected for virological monitoring. Initially, day-old chicks had high mean MDA titres (9 + 0.9 log2). The MDA half-life was >7 and <7 days, respectively, for unvaccinated and vaccinated birds. Group III showed the highest post-vaccination humoral immune response and seroconversion rate. The highest protection rate against morbidity (80–90%) and mortality (90–90%) was obtained in Group III after challenge at D28 and D35, respectively, as compared to Group I (70–70%) and (80–90%) and Group II (0–0%) and (30–30%). Groups I and III had lower number of shedder birds. The vaccination regime with prime/boost conferred the highest and earliest protection, and can hence be recommended for the broiler production sector in endemic and high HPAI H5N1 challenge areas.

Protection against canine parvovirus type 2 infection in puppies by colostrum-derived antibodies.

During the first weeks of life puppies remain protected against canine parvovirus type 2 (CPV2) infection thanks to maternally derived antibodies (MDA) absorbed with colostrum after birth. The objective of the present study was to present the variability in CPV2-specific passive immune transfer and its consequences in puppies naturally exposed to the parvovirus. Seventy-nine puppies from one breeding kennel were included in the study at birth and followed until 56d of age. Once per week the MDA titre for CPV2 specific antibodies was determined in blood. Viral excretion was also evaluated on a rectal swab by CPV2 PCR assay and puppies were weighed to determine growth rate. At 2d of age, thirty-four out of seventy-nine puppies (43%) had MDA ≤1:160 (designed group A) and forty-five puppies (57%) had greater MDA titres (designed group B). The level of absorbed maternal antibodies was shown to be associated with breed size and growth rate during the first 48h of life. The MDA level declined with age in all cases; however, the proportion of puppies with the antibody level considered as protective against CPV2 infection was significantly higher in group B compared with A from day 2 until 42. Among all puppies surviving until 56d of age, sixty-seven out of seventy (95·7%) underwent CPV2 infection. However, puppies from group A excreted CPV2 significantly earlier than puppies from group B. The present study demonstrates the link between passive immune transfer, in terms of level of specific MDA absorbed, and length of the protection period against parvovirus infection in weaning puppies.

Influence of age on the effectiveness of PCV2 vaccination in piglets with high levels of maternally derived antibodies

Two field studies were conducted to investigate the influence of age on the efficacy of vaccination against Porcine Circovirus Diseases (PCVD) in animals with high levels of maternally derived antibodies (MDA). A total of 416 piglets (Study 1) and 600 piglets (Study 2) were randomly allocated to one of three groups. Two groups in each study received a single dose of a PCV2 subunit vaccine, one group at 1 week old and the other at 3 weeks of age. The third group was left untreated. Animals vaccinated at 3 weeks of age showed a significantly higher average daily weight gain and significantly reduced viraemia following PCV2 infection than the respective control groups. This difference was not observed in pigs vaccinated at 1 week of age. Furthermore, only animals vaccinated at 3 weeks of age showed an increased serological response and a higher frequency of IgM-positive animals compared with controls. The data indicated that PCV2 vaccination in the presence of high MDA levels is efficacious when used in 3-week old but not in 1-week old pigs. As the range of MDA titres of pigs vaccinated at both 1 and 3 weeks of age were comparable, the data suggest that PCV2 vaccine efficacy was independent of the level of MDA. It appears that other age-related factors affecting the active and passive transfer of immunity may perhaps have interfered with the efficacy of the vaccine in 1-week old piglets. These findings have implications for future PCV2 vaccine testing and administration strategies.

Vaccination against Feline Panleukopenia: implications from a field study in kittens

BackgroundFeline Panleukopenia (FPL) is a serious disease of cats that can be prevented by vaccination. Kittens are routinely vaccinated repeatedly during their first months of life. By this time maternally derived antibodies (MDA) can interfere with vaccination and inhibit the development of active immunity. The efficacy of primary vaccination under field conditions was questioned by frequent reports to the Paul-Ehrlich-Institut on outbreaks of FPL in vaccinated breeding catteries. We therefore initiated a field study to investigate the development of immunity in kittens during primary vaccination against FPL.64 kittens from 16 litters were vaccinated against FPL at the age of 8, 12 and 16 weeks using three commercial polyvalent vaccines. Blood samples were taken before each vaccination and at the age of 20 weeks. Sera were tested for antibodies against Feline Panleukopenia Virus (FPV) by hemagglutination inhibition test and serum neutralisation assay in two independent diagnostic laboratories.ResultsThere was a good correlation between the results obtained in different laboratories and with different methods. Despite triple vaccination 36.7% of the kittens did not seroconvert. Even very low titres of MDA apparently inhibited the development of active immunity. The majority of kittens displayed significant titres of MDA at 8 and 12 weeks of age; in some animals MDA were still detected at 20 weeks of age. Interestingly, the vaccines tested differed significantly in their ability to overcome low levels of maternal immunity.ConclusionsIn the given situation it is recommended to quantify antibodies against FPV in the serum of the queen or kittens before primary vaccination of kittens. The beginning of primary vaccination should be delayed until MDA titres have declined. Unprotected kittens that have been identified serologically should be revaccinated.

Passive Protection Afforded by Maternally-Derived Antibodies in Chickens and the Antibodies' Interference with the Protection Elicited by Avian Influenza–Inactivated Vaccines in Progeny

Systematic vaccination can be applied when a disease has become enzootic in a country or region. The final goal of the approach is to control or eradicate the disease within the country. This is a long-term vaccination plan that could be applied nationwide to all commercial and backyard poultry. However, after several months of vaccination in enzootic areas, maternally derived antibody (MDA) is present in young chicks, providing some protection and/or interference with vaccination. The aim of this study was to evaluate the level of protection afforded by MDA against challenge with highly pathogenic avian influenza virus (HPAIV), and its suspected interference with current inactivated vaccines in broilers under controlled laboratory conditions. In the first set of experiments, broilers were vaccinated with inactivated vaccines containing H5N2 subtype antigens in the presence or absence of homologue MDAs and challenged with a clade 2.2 H5N1 HPAIV. In the second set of experiments, day-old broilers, either with or without avian influenza MDA, received a regular-type monovalent H5N2 AI vaccine (0.5 ml) or a concentrated (0.2 ml) AL-Newcastle disease virus combined inactivated vaccine subcutaneously. They were then challenged at 11 or 35 days of age. In conclusion, our results indicate that protection induced by day-old administration of inactivated vaccine (regular or concentrated) in the presence or absence of MDA to H5N2 AIV induces poor protection against challenge with H5N1 HPAIV and should not be recommended. Based on our results, vaccination of MDA-positive chickens at a later age (10 days) seems to be a valuable recommendation, although MDAs may still interfere with vaccination to a lesser extent because they are present up to 3 wk posthatch. Therefore, in areas with high infection pressure, when possible, two vaccinations are recommended for optimal protection. Also, it might be advisable to take into account day-old AI MDA titers when one is determining the optimal age of vaccination.

The Use of Linear Mixed Models to Estimate Optimal Vaccination Timing for Infectious Bursal Disease in Broilers in Paraguay

The objectives of this study were (1) to fit linear mixed models for Maternally Derived Antibody (MDA) values for estimating optimal days of age for Infectious Bursal Disease (IBD) vaccination in broiler chicks and (2) to evaluate how optimal vaccination timing estimates varied, based on the field data collected in Paraguay. The MDA titres were measured by Enzyme-linked Immunosorbent Assay (ELISA) with sera collected from 20 chicks per flock (n = 14) at 1, 8 and 15 days of age. Both Restricted Maximum-likelihood (REML) and Markov Chain-Monte Carlo (MCMC) estimation methods were used to fit linear mixed models for the dependent variable log-transformed MDA. There is a slight dissimilarity of each estimate between the two models because of the difference in mathematical algorithms and handling method of missing data. The study flocks with the earliest and latest estimated optimal timing for vaccination had a mean days of age of 15.1 [95% Bayesian Credible Interval (BCI): 13.3-17.0] and 23.7 [95% BCI: 21.7-25.7], respectively. This variation could be partly explained by a limited understanding of the true biological variability representing the variety of factors affecting MDA in the study chicks. Although the results of the study can be used as a benchmark to establish IBD vaccination programmes in the study area, it is recommended for estimating optimal IBD vaccination timing to measure the MDA level by ELISA tests on a routine basis.

The influence of maternal antibody and age of calves on effective vaccination against Leptospira interrogans serovar hardjo

Twelve seronegative cows were vaccinated with an experimental bivalent Leptospira interrogans serovars hardjo and pomona vaccine late in their first pregnancy. Calves born of these dams were divided into 4 equal groups that received this vaccine at 4, 6, 10 and 18 weeks of age, respectively. Before vaccination the group geometric mean titres of maternally-derived circulating antibodies ranged from 2 to 25 for the microscopic agglutination (MA) test and 3 to 35 for enzyme-linked immunosorbent assay (ELISA) using a serovar hardjo outer envelope antigen. Post-vaccination peak titres were 645 to 1612 for MA and 562 to 1037 for ELISA, respectively. Calves vaccinated at the youngest age, had the highest pre-vaccination circulating maternal antibody titres, but showed the smallest rise in post-vaccination antibody titres. Circulating maternal antibody was detected in calves up to 13 weeks of age. All immunised calves were protected against a virulent challenge with serovar hardjo type Hardjobovis, regardless of their age or maternally-derived antibody titres. These findings indicate that calves as young as 4 weeks old, vaccinated in the presence of maternally-derived antibody, can be fully protected against homologous virulent challenge.

Intranasal vaccination of pigs against Aujeszky's disease: protective immunity at 2 weeks, 2 months and 4 months after vaccination in pigs with maternal antibodies

The purpose of the study was to evaluate the short- and long-term immunity after intranasal vaccination in pigs with maternally derived antibodies (MDA). In two experiments, 10-week-old pigs with moderate MDA titres against Aujeszky's disease virus (ADV) were vaccinated intranasally with the Bartha strain of ADV to evaluate the protective immunity conferred at 2 weeks, 2 months and 4 months after vaccination. Protection was evaluated on the basis of severity of clinical signs, periods of fever and growth arrest, and duration and amount of virus excreted after challenge with a virulent ADV. During the first 2–3 weeks after vaccination, antibodies to ADV continued to decline as in unvaccinated control pigs. After that, antibody titres stabilized or gradually increased. At 2 weeks, 2 months and 4 months after vaccination, vaccinated pigs were significantly better protected than unvaccinated controls. The vaccinated pigs challenged 2 weeks after vaccination hardly developed any sign of disease. Mild signs of Aujeszky's disease and a growth arrest period of 5 days were observed in vaccinated pigs challenged 2 months after vaccination, whereas vaccinated pigs challenged 4 months after vaccination developed severe signs of disease and a growth arrest period of 13 days. Vaccinated pigs challenged 2 weeks after vaccination did not excrete challenge virus, and pigs challenged 2 or 4 months after vaccination excreted far less virus than unvaccinated controls. The results demonstrate that intranasal ADV vaccination of pigs with moderate MDA titres protected them from 2 weeks to at least 4 months after vaccination. Immunity steadily declined, however, after vaccination.

Intranasal vaccination of pigs against Aujeszky's disease. 4. Comparison with one or two doses of an inactivated vaccine in pigs with moderate maternal antibody titres

• Intranasal (IN) vaccination of pigs with low levels of maternally-derived antibody (MDA) has previously been shown to confer good protection against challenge with virulent Aujeszky's disease virus (ADV). The objective of the present study was to determine the efficacy of IN vaccination with an attenuated ADV, in comparison with that of an inactivated vaccine given parenterally, in pigs with higher MDA titres at the time of vaccination. • In one experiment, vaccinations were done at 6 weeks of age, and in another experiment pigs were vaccinated at 4 and/or 9 weeks of age. Two months after (the last) vaccination pigs were challenged intranasally with a virulent ADV. Protection was evaluated on the basis of mortality, periods of growth arrest, fever and virus shedding after challenge. • The presence of MDA markedly depressed the serum-neutralizing antibody response after vaccination. Sensitisation occured after parenteral vaccination with an inactivated vaccine despite high MDA levels. Although the intranasally-vaccinated pigs had lower levels of neutralizing antibody at the time of challenge, they were significantly better protected than pigs given 1 or 2 doses of the inactivated vaccine. • Comparing the present results with those of a previous study, it appears that the efficacy of parenteral as well as intranasal ADV vaccination decreases with increasing levels of MDA at the time of vaccination.

The effect of maternally derived antibodies on the response of calves to vaccination against foot and mouth disease.

Studies were carried out in South America to assess the effect of maternally derived antibody (MDA) on the responsiveness of calves to FMD vaccination. It was found that calves with MDA did not merely fail to respond to vaccination, but that their serum titres were depressed. This depression was proportional to the level of pre-existing MDA at the time of vaccination and following primary vaccination it persisted for a least 60 days. High MDA titres interfered with both primary and secondary responses. Animals with relatively low MDA titres were able to respond to vaccination, or at least to be sensitized so that on revaccination they showed a satisfactory response. The half-life of MDA was shown to be approximately 22 days, suggesting that under field conditions significant MDA titres are likely to persist for 4-5 months. A trial carried out in Brazil in which the primary course of two inoculations, 4 weeks apart, was initiated when the calves were 5-6 months of age, resulted in the reduction of FMD in the calf population from 11% to 0.9% over a 12-month period. The use of vaccination programmes of this type to lessen the incidence of FMD in young bovines is discussed.