Presence Of Maternally Derived Antibodies Research Articles

Potential Interference of Maternally Derived Antibodies (MDA) of Commercial Broiler Chicks on the Efficacy of Different Vectored –ND Vaccines

Maternally derived antibodies (MDA) are a major problem for the application of NDV-vectored vaccines in commercial chickens with high levels of MDA, which could impair its efficacy. In this study, we assessed the effectiveness of different commercial vectored ND in broilers chicks with MDA against local heterologous NDV genotype VII. For this purpose, Two hundred and forty one day old chicks were divided into eight groups (30 chicks/group) (G1, G2, G3, G4, G5, G6 and G7) vaccinated with four different recombinant ND vaccines using different vaccination scheme. In addition, Group 8 (30 chicks) kept as a control non-vaccinated group. Efficacy of this type of vaccine is evaluated routinely by vaccination-challenge test. ELISA test were used for detection antibodies from collected sera of all chickens groups. Challenge test were applied at 31th day's old age of chickens. To calculate viral Shedding, cloacal swabs were collected from all groups and examined by real time RT-PCR. Obtained results for G8 (control) was recorded high antibody titer at one day but decreased gradually till become negative at 24 day old. While vaccinated groups exhibited antibody titers at 38 days old which were 3.6, 3.7, 4, 3.7, 3.66, 3.77, and 3.3 for G1, G2, G3, G4, G5, G6 and G7, respectively. Protection% of vectored ND vaccines groups ranged from 80 to 95 % despite inactivated ND vaccine recorded 60%. It was concluded that the recombinant ND vectored vaccines more potent than inactivated one in broiler chickens with MDA. Administration of rFowl-Pox+ND vaccine at 10 day exhibited higher immune response and conferred more protection and reduction of viral shedding in comparison to vaccinated at hatchery. Using rHVT+ND vaccine in one day old chicks confer optimum immune response and protection% in presence of MDA. Prime-boost vaccination strategy can overcome the problem of MDA in broiler chickens vaccination. So, it was recommended to measure the level of MDA in offspring to determine the ideal time for vaccination

Comparative efficacy evaluation of different CSF vaccines in pigs with CSF maternally derived antibodies

Classical swine fever (CSF) is a highly contagious and important swine disease in China. Sporadic outbreaks with mild clinical signs are still being reported despite massive vaccination with the CSF C-strain vaccine. One possible reason for vaccine failure could be interference from maternally derived antibodies (MDAs) during vaccination in the field. The aim of this study was to evaluate the efficacy of different CSF vaccines in the presence of MDAs and to assess the different vaccination schemes in the field. The results demonstrated that vaccination with a single dose of C-strain-PK vaccine protected pigs against severe clinical signs and significantly reduced viremia. The impact of MDAs was negligible. The interference was also mild during a prime and boost vaccination scheme using the C-strain-ST vaccine. In contrast, a significant influence of MDAs on the efficacy of the subunit E2 vaccine in a one-dose vaccination scheme was observed, with pigs showing severe clinical signs, CSF-associated death, typical pathological lesions and a high level of viremia after challenge, despite robust E2 antibody induction. A field vaccination and challenge study further confirmed the superior effectiveness of a single dose of C-strain-PK vaccine in the presence of MDAs in comparison to a routine prime and boost vaccination scheme applied in the field, with pigs having fever, chronic signs, significant viremia and shedding after challenge. Delaying the vaccination time from the age of 28 days to 45 days, when MDA was low, was beneficial for improving the clinical protection and immunity induced by vaccines. Altogether, the results presented here emphasize that a high-quality vaccine and a scientific design of the vaccination scheme based on serological surveillance are essential pillars to control and eliminate CSF in China.

Immunization with a mucosal, post-fusion F/G protein-based polyanhydride nanovaccine protects against BRSV infection in neonatal calves

Abstract Human respiratory syncytial virus (HRSV) is a leading cause of severe acute lower respiratory tract (LRT) disease in young children worldwide. Currently, there is no approved vaccine for HRSV. Bovine RSV (BRSV) is closely related to HRSV and is the cause of severe acute LRT disease in young cattle. A neonatal calf model presents an opportunity to test HRSV vaccines and study a naturally susceptible host-pathogen interaction similar to HRSV infection. We tested the efficacy of a polyanhydride nanoparticle-vaccine (nanovaccine) encapsulating the post-fusion F and G proteins from BRSV and CpG adjuvant in neonatal calves with maternally-derived antibodies (MDA). A prime-boost immunization of neonatal calves with the BRSV post-fusion F/G CpG nanovaccine induced clinical protection in the presence of MDA. Vaccinated calves developed moderate or no clinical symptoms and were mostly protected from virus-associated lung pathology compared to unvaccinated controls. Calves that received a mucosal/systemic nanovaccine immunization had complete virological protection against BRSV infection in the lungs, which correlated with BRSV-specific immune responses in the bronchoalveolar lavage. Vaccination with the nanovaccine induced anamnestic BRSV-specific IgA titers in the lungs and systemic T cell responses with BRSV-specific CD4+ T cell proliferation and antigen-specific IL-17 and IFNγ secretion. Overall, the BRSV post-fusion F/G CpG nanovaccine is a promising candidate for further studies to protect neonatal calves and infants from RSV infection.

Immune B cell responsiveness to single-dose intradermal vaccination against Mycoplasma hyopneumoniae

Mycoplasma hyopneumoniae is a major pathogen affecting pig herds and vaccination is the most utilized approach, despite providing partial protection. Age at vaccination, the delivery route, and vaccination protocol can influence vaccine efficacy. The influence of age and the presence of maternally-derived antibodies at vaccination on single-dose needle-less intradermal (ID) administration of an inactivated bacterin-based vaccine (Porcilis® M Hyo ID Once) were assessed in conventional pigs under field conditions. The induction of IgA+ and IgG+ B cell responses and the expression of the activation markers TLR2, TLR7, CCR9, and CCR10 were determined in PBMC. Vaccination at 4 weeks efficiently elicited an anamnestic antibody response associated with TLR2 and TLR7 upregulation. Although animals vaccinated at 1 week did not show seroconversion and a recall response upon infection, the responsiveness of Mycoplasma-recalled IgA+ B cells suggests the activation of mucosal immune cells after vaccination and infection. Vaccination at 1 week induced TLR2, TLR7, and CCR9 upregulation, suggesting the potential for systemic and local activation of immune cell trafficking between blood and target tissues. Vaccination at 4 weeks induced a CCR10 increase, suggesting that recalled IgA+ and IgG+ B cells can display an activated status upon infection. The antibody response after Mycoplasma infection in 4-week-old ID-vaccinated pigs was associated with TLR2 and CCR10 increases, confirming the potential use of this vaccination schedule for the safe and efficient delivery of single-dose M. hyopneumoniae vaccines. ID vaccination, especially at 4 weeks, was associated with a great degree of protection against enzootic pneumonia (EP)-like lung lesions.

Influenza A Virus in Swine: Epidemiology, Challenges and Vaccination Strategies.

Influenza A viruses cause acute respiratory infections in swine that result in significant economic losses for global pig production. Currently, three different subtypes of influenza A viruses of swine (IAV-S) co-circulate worldwide: H1N1, H3N2, and H1N2. However, the origin, genetic background and antigenic properties of those IAV-S vary considerably from region to region. Pigs could also have a role in the adaptation of avian influenza A viruses to humans and other mammalian hosts, either as intermediate hosts in which avian influenza viruses may adapt to humans, or as a “mixing vessel” in which influenza viruses from various origins may reassort, generating novel progeny viruses capable of replicating and spreading among humans. These potential roles highlight the importance of controlling influenza A viruses in pigs. Vaccination is currently the main tool to control IAV-S. Vaccines containing whole inactivated virus (WIV) with adjuvant have been traditionally used to generate highly specific antibodies against hemagglutinin (HA), the main antigenic protein. WIV vaccines are safe and protect against antigenically identical or very similar strains in the absence of maternally derived antibodies (MDAs). Yet, their efficacy is reduced against heterologous strains, or in presence of MDAs. Moreover, vaccine-associated enhanced respiratory disease (VAERD) has been described in pigs vaccinated with WIV vaccines and challenged with heterologous strains in the US. This, together with the increasingly complex epidemiology of SIVs, illustrates the need to explore new vaccination technologies and strategies. Currently, there are two different non-inactivated vaccines commercialized for swine in the US: an RNA vector vaccine expressing the HA of a H3N2 cluster IV, and a bivalent modified live vaccine (MLV) containing H1N2 γ-clade and H3N2 cluster IV. In addition, recombinant-protein vaccines, DNA vector vaccines and alternative attenuation technologies are being explored, but none of these new technologies has yet reached the market. The aim of this article is to provide a thorough review of the current epidemiological scenario of IAV-S, the challenges faced in the control of IAV-S infection and the tools being explored to overcome those challenges.

Acute Influenza A virus outbreak in an enzootic infected sow herd: Impact on viral dynamics, genetic and antigenic variability and effect of maternally derived antibodies and vaccination.

Influenza A virus (IAV) is a highly contagious pathogen in pigs. Swine IAV (swIAV) infection causes respiratory disease and is thereby a challenge for animal health, animal welfare and the production economy. In Europe, the most widespread strategy for controlling swIAV is implementation of sow vaccination programs, to secure delivery of protective maternally derived antibodies (MDAs) to the newborn piglets. In this study we report a unique case, where a persistently swIAV (A/sw/Denmark/P5U4/2016(H1N1)) infected herd experienced an acute outbreak with a new swIAV subtype (A/sw/Denmark/HB4280U1/2017(H1N2)) and subsequently decided to implement a mass sow vaccination program. Clinical registrations, nasal swabs and blood samples were collected from four different batches of pigs before and after vaccination. Virus isolation, sequencing of the virus strain and hemagglutinin inhibition (HI) tests were performed on samples collected before and during the outbreak and after implementation of mass sow vaccination. After implementation of the sow mass vaccination, the time of infection was delayed and the viral load significantly decreased. An increased number of pigs, however, tested positive at two consecutive sampling times indicating prolonged shedding. In addition, a significantly smaller proportion of the 10-12 weeks old pigs were seropositive by the end of the study, indicating an impaired induction of antibodies against swIAV in the presence of MDAs. Sequencing of the herd strains revealed major differences in the hemagglutinin gene of the strain isolated before- and during the acute outbreak despite that, the two strains belonged to the same HA lineage. The HI tests confirmed a limited degree of cross-reaction between the two strains. Furthermore, the sequencing results of the hemagglutinin gene obtained before and after implementation of mass sow vaccination revealed an increased substitution rate and an increase in positively selected sites in the globular head of the hemagglutinin after vaccination.

Vaccination of broilers against Newcastle disease in the presence of maternally derived antibodies.

The aim of this study was to evaluate the efficacy of a live attenuated vaccine against Newcastle disease in broilers with different levels of maternally derived antibodies (MDA). While vaccination remains the single most important means for controlling Newcastle disease, presence of MDA may interfere with the vaccination of young birds and decrease the efficacy of the vaccine. Day-old chicks with variable levels of MDA (negative, low and high) were vaccinated with a live attenuated vaccine against Newcastle disease. Three most commonly used inoculation routes were compared; oculonasal, spray and oral (drinking water). Onset and duration of immunity were measured by serology and challenge with virulent virus. Immune response in vaccinated MDA-positive birds was delayed in comparison with SPF controls. Protection was well established already at 14days post vaccination in SPF birds while in MDA-positive birds it was 1-2weeks delayed and was lower throughout the study. Non-vaccinated MDA-positive birds lost passive protection completely at 3-4weeks of age and were significantly more susceptible to challenge than vaccinated hatch mates at all test points. The protection rate increased in vaccinated birds towards the end of the experiment and reached 70-100 % at the last test points (35-42days of age). Correlation of haemagglutination inhibition (HI) titre vs. protection rate revealed the importance of cellular and local immunity as most of the vaccinated birds with low HI titre were protected, contrary to their unvaccinated hatch mates with the same HI titre. Oculonasal route seems to provide slightly better protection than the other two routes. Although immune protection in vaccinated MDA-positive birds may be decreased or delayed, vaccination still provides high protection against ND challenge in comparison with the unvaccinated hatch mates. The degree of interference seems to be proportional to the level of MDA. Vaccination schedules therefore need to be designed according to the immune status of the flock.

Influential factors inducing suboptimal humoral response to vector-based influenza immunisation in Thoroughbred foals

ContextNumerous equine influenza (EI) epizooties are reported worldwide. EI vaccination is the most efficient methods of prevention. However, not all horses develop protective immunity after immunisation, increasing the risk of infection and transmission. ObjectivesThis field study aimed to understand the poor response to primary EI vaccination. Study designThe EI antibody response was measured in 174 Thoroughbred foals set in 3 stud farms (SF#1 to SF#3) over a 2years period. All foals were immunised with a commercial recombinant canarypox-based EI vaccine. Sera were tested by single radial haemolysis against the A/equine/Jouars/4/06 EIV strain (H3N8) at the time of the first vaccination (V1), 2weeks and 3months after the second immunisation (V2), 2days and 3months after the third immunisation (V3). ResultsThe frequency of poor-responders (no detectable antibody titres) was surprisingly elevated after V2 (56.8%), increased to 81.7% at V2+3months and reached 98.6% at V3. The frequency of poor-responder was still 19.2%, 3months after V3. Two independent influential factors were identified. The short (V2+2weeks) and mid-term (V2+3months, V3+3months) antibody levels were positively correlated to the age at V1 (p-value=0.003, 0.031 and 0.0038, respectively). Presence of maternally-derived antibodies (MDA) at V1 was negatively correlated with antibody levels after V3 only (p-value=0.0056). Given that SF#1 antibody response was below clinical protective levels at all-time points studied, the annual boost immunisation (V4) was brought forward by 7.0±1.1months. V1 was delayed by 7weeks the following year, which significantly increased short- and mid-term antibody titres (p-value=9.9e−07 and 2.31e−07, respectively). ConclusionThe age and MDA at first immunisation with the canarypox-based IE vaccine play an independent role in the establishment of antibody levels. This study also highlights the benefit provided by serological surveillance to evaluate herd immunity and to implement corrective management/vaccination measures.

Influence of maternally-derived antibodies on live attenuated influenza vaccine efficacy in pigs

Vaccination during pregnancy is practiced in swine farms as one measure to control swine influenza virus (SIV) infection in piglets at an early age. Vaccine-induced maternal antibodies transfer to piglets through colostrum and stabilize the herd: however, maternally derived antibodies (MDA) interfere with immune response following influenza vaccination in piglets at the later stage of life. In addition, MDA is related to enhanced respiratory disease in SIV infection. Previously, we have developed a bivalent live attenuated influenza vaccine (LAIV) which harbors both H1 and H3 HAs. We demonstrated vaccination of this LAIV provided protection to homologous and heterologous SIV infection in pigs. In this study we aimed to investigate the influence of MDA on LAIV efficacy. To this end, SIV sero-negative sows were vaccinated with a commercial vaccine. After parturition, nursery piglets were vaccinated with LAIV intranasally or intramuscularly, and were then challenged with SIV. We report that MDA hampered serum antibody response induced by intramuscular vaccination but not by intranasal vaccination of the LAIV. Viral challenge in the presence of MDA caused exacerbated respiratory disease in unvaccinated piglets. In contrast, all LAIV vaccinated piglets were protected from homologous viral infection regardless of the route of vaccination and the presence of MDA. Our results demonstrated that LAIV conferred protection in the presence of MDA without inciting exacerbated respiratory disease.

Efficacy of CSF vaccine CP7_E2alf in piglets with maternally derived antibodies

There is a need for live DIVA (differentiating infected from vaccinated animals) vaccines against classical swine fever (CSF). The aim of this study was to investigate whether vaccination with the chimeric pestivirus vaccine CP7_E2alf is efficacious to protect young piglets born from vaccinated sows, thus with maternally derived antibodies (MDAs). Groups of 10 piglets each, with or without MDAs, were vaccinated either intramuscularly (IM), at an age of 3 or 6 weeks, or orally (OR), at an age of 6 weeks. Five piglets of each group were challenged with CSFV strain Koslov and protection against clinical disease, virus shedding and transmission were studied.Vaccination with CP7_E2alf, both in the presence of MDA's and in piglets without MDA's, protected against severe clinical signs, but virus shedding from most inoculated piglets and transmission to contact pigs was observed. However, virus transmission in the vaccinated piglets was significantly reduced as compared to non-vaccinated piglets, although the reproduction ratio's R calculated from the results in the vaccinated pigs from our study were not yet significantly below 1. The efficacy of vaccination with CP7_E2alf in the presence of MDAs (RIMvac=0.8, RORvac=0.4) seemed to be slightly less as compared to vaccination in the absence of MDAs (RIMvac=0.2, RORvac=0).On a population level, the results suggest that the CP7_E2alf vaccine is an effective tool in the control and eradication of CSF and, moreover, can be applied for both IM and oral use for young age groups, with MDAs having a limited effect on the efficacy.

Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies

Live-attenuated influenza virus (LAIV) prime-boost vaccination previously conferred protection against heterologous H3N2 swine influenza challenge, including in piglets with maternally derived antibodies (MDA). Conversely, a whole-inactivated virus (WIV) vaccine was associated with enhanced disease. This study was aimed at identifying immune correlates of cross-protection. Piglets with and without MDA received intramuscular adjuvanted WIV or intranasal LAIV, and were challenged with heterologous H3N2. WIV induced cross-reactive IgG, inhibited by MDA, and a moderate T cell response. LAIV elicited mucosal antibodies and T cells cross-reactive to the heterologous challenge strain. The presence of MDA at LAIV vaccination blocked lung and nasal antibody production, but did not interfere with T cell priming. Even without mucosal antibodies, MDA-positive LAIV vaccinates were protected, indicating a likely role for T cells. Based on the data, one LAIV dose can induce cell-mediated immunity against antigenically divergent H3N2 influenza virus despite passive antibody interference with humoral immune responses.

Swine influenza virus vaccine serologic cross‐reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011–2012 H3N2v

Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross-reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA.

Live Attenuated Influenza Vaccine Provides Superior Protection from Heterologous Infection in Pigs with Maternal Antibodies without Inducing Vaccine-Associated Enhanced Respiratory Disease

Control of swine influenza A virus (IAV) in the United States is hindered because inactivated vaccines do not provide robust cross-protection against the multiple antigenic variants cocirculating in the field. Vaccine efficacy can be limited further for vaccines administered to young pigs that possess maternally derived immunity. We previously demonstrated that a recombinant A/sw/Texas/4199-2/1998 (TX98) (H3N2) virus expressing a truncated NS1 protein is attenuated in swine and has potential for use as an intranasal live attenuated influenza virus (LAIV) vaccine. In the present study, we compared 1 dose of intranasal LAIV with 2 intramuscular doses of TX98 whole inactivated virus (WIV) with adjuvant in weanling pigs with and without TX98-specific maternally derived antibodies (MDA). Pigs were subsequently challenged with wild-type homologous TX98 H3N2 virus or with an antigenic variant, A/sw/Colorado/23619/1999 (CO99) (H3N2). In the absence of MDA, both vaccines protected against homologous TX98 and heterologous CO99 shedding, although the LAIV elicited lower hemagglutination inhibition (HI) antibody titers in serum. The efficacy of both vaccines was reduced by the presence of MDA; however, WIV vaccination of MDA-positive pigs led to dramatically enhanced pneumonia following heterologous challenge, a phenomenon known as vaccine-associated enhanced respiratory disease (VAERD). A single dose of LAIV administered to MDA-positive pigs still provided partial protection from CO99 and may be a safer vaccine for young pigs under field conditions, where dams are routinely vaccinated and diverse IAV strains are in circulation. These results have implications not only for pigs but also for other influenza virus host species.

Effect of age and maternally-derived antibody status on humoral and cellular immune responses to vaccination of pigs against Erysipelothrix rhusiopathiae

The effects of age and maternally-derived antibodies (MDA) on the immune response to Erysipelothrix rhusiopathiae were investigated in piglets orally vaccinated with a live E. rhusiopathiae vaccine at 6, 8 or 10 weeks of age. Seroconversion, determined by ELISA, was evident in MDA positive piglets vaccinated at 8 or 10 weeks of age and in all MDA negative vaccinates. Two weeks after vaccination in the presence of MDA, a T cell response, measured by a lymphocyte proliferation assay, was observed in 25% of piglets vaccinated at 6 weeks of age and in 100% of piglets vaccinated at 8 or 10 weeks of age. The post-vaccinal response to E. rhusiopathiae was more strongly influenced by the maternal antibody status of the piglet at the time of vaccination than the age of the piglet.

Bovine respiratory syncytial virus ISCOMs—Immunity, protection and safety in young conventional calves

Bovine respiratory syncytial virus (BRSV) is a major cause of bronchiolitis and pneumonia in cattle and causes yearly outbreaks with high morbidity in Europe. Commercial vaccines against this virus needs improvement of efficacy, especially in calves with BRSV-specific maternally derived antibodies (MDA). We previously reported that an experimental BRSV-ISCOM vaccine, but not a commercial vaccine, induced strong clinical and virological protection in calves with MDA, immunized at 7-15 weeks of age. The aim of the present study was to characterize the immune responses, as well as to investigate the efficacy and safety in younger animals, representing the target population for vaccination. Four groups of five 3-8 week old calves with variable levels of BRSV-specific MDA were immunized s.c. twice at a 3 weeks interval with (i) BRSV immunostimulating complexes (BRSV-ISCOMs), (ii) BRSV-protein, (iii) adjuvant, or (iv) PBS. All calves were challenged with virulent BRSV by aerosol 2 weeks later and euthanized on day 6 after infection. The cellular and humoral responses were monitored as well as the clinical signs, the viral excretion and the pathology following challenge. Despite presence of MDA at the time of the immunization, only a minimum of clinical signs were observed in the BRSV-ISCOM group after challenge. In contrast, in all control groups, clinical signs of disease were observed in most of the animals (respiratory rates up to 76min(-1) and rectal temperatures up to 41°C). The clinical protection was associated to a highly significant reduction of virus replication in the upper and lower respiratory tract of calves, rapid systemic and local antibody responses and T helper cell responses dominated by IFNγ production. Animals that did not shed virus detectable by PCR or cell culture following challenge possessed particularly high levels of pulmonary IgA. The protective immunological responses to BRSV proteins and the ability to overcome the inhibiting effect of MDA were dependent on ISCOM borne antigen presentation.

Evaluation of humoral and antigen-specific T-cell responses after vaccination of pigs against pseudorabies in the presence of maternal antibodies

In this study the influence of maternal immunity against pseudorabies virus (PRV) on the development of humoral and T-cell mediated immune (CMI) responses was investigated under the experimental condition. Pigs born to immune sows were vaccinated with gE-deleted vaccine according to five different schedules. Peripheral blood mononuclear cells (PBMC), collected after vaccination, were used for PRV-induced lymphocyte proliferation assay (LPA). Antibodies to the gB and gE of PRV in serum were determined using ELISA kits. Maternally derived antibodies (MDA) in the serum of unvaccinated piglets born to immune sows were above the level considered to be positive until about 10–11 weeks of life. The active humoral as well as CMI responses was the highest in group vaccinated at 10 and 14 weeks of age. The results of this study suggest that MDA may disturb or even block development of active humoral response. Early priming of T-cells with attenuated gE-deleted PRV vaccine in the presence of MDA could be successful, but obtaining a long-term cellular immunity at least one booster is required.

The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination

This study investigated the efficacy of a bivalent swine influenza virus (SIV) vaccine in piglets challenged with a heterologous H1N1 SIV isolate. The ability of maternally derived antibodies (MDA) to provide protection against a heterologous challenge and the impact MDA have on vaccine efficacy were also evaluated. Forty-eight MDA + pigs and 48 MDA − pigs were assigned to 8 different groups. Vaccinated pigs received two doses of a bivalent SIV vaccine at 3 and 5 weeks of age. The infected pigs were challenged at 7 weeks of age with an H1N1 SIV strain heterologous to the H1N1 vaccine strain. Clinical signs, rectal temperature, macroscopic and microscopic lesions, virus excretion, serum and local antibody responses, and influenza-specific T-cell responses were measured. The bivalent SIV vaccine induced a high serum hemagglutination-inhibition (HI) antibody titer against the vaccine virus, but antibodies cross-reacted at a lower level to the challenge virus. This study determined that low serum HI antibodies to a challenge virus induced by vaccination with a heterologous virus provided protection demonstrated by clinical protection and reduced pneumonia and viral excretion. The vaccine was able to prime the local SIV-specific antibody response in the lower respiratory tract as well as inducing a systemic SIV-specific memory T-cell response. MDA alone were capable of suppressing fever subsequent to infection, but other parameters showed reduced protection against infection compared to vaccination. The presence of MDA at vaccination negatively impacted vaccine efficacy as fever and clinical signs were prolonged, and unexpectedly, SIV-induced pneumonia was increased compared to pigs vaccinated in the absence of MDA. MDA also suppressed the serum antibody response and the induction of SIV-specific memory T-cells following vaccination. The results of this study question the effectiveness of the current practice of generating increased MDA levels through sow vaccination in protecting piglets against disease.

Determinants of infant responses to vaccines in presence of maternal antibodies

Presence of maternally-derived antibodies at time of immunization is known to often interfere with active infant immunization, although with variable degrees of clinical significance. In order to progressively decipher the rules that form the basis for these inhibitory effects on infant vaccine responses, two antigens (measles, tetanus) and various antigen presentation systems were evaluated in murine early life immunization models either in absence or presence of maternal antibodies. Both conventional (proteins, conjugate vaccines) and new (live viral vectors, DNA plasmids) antigen presentation systems were found to be similarly susceptible to the inhibitory influence of maternal antibodies. Factors emerging as crucial determinants of maternal antibody-mediated effects on responses to both live and non-live vaccines include (i) the level of maternal antibodies present at immunization, (ii) the use of distinct vaccines in mothers and pups and (iii) their distinct influence on B cell and T cell vaccine responses.

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.