Specific Maternal Antibodies Research Articles

Isolation, Molecular, and Histopathological Patterns of a Novel Variant of Infectious Bursal Disease Virus in Chicken Flocks in Egypt.

After an extended period of detecting classical virulent, attenuated, and very virulent IBDV, a novel variant (nVarIBDV) was confirmed in Egypt in this study in 18, IBD vaccinated, chicken flocks aged 19-49 days. Partial sequence of viral protein 2 (VP2) [219 aa, 147-366, resembling 657 bp] of two obtained isolates (nos. 3 and 4) revealed nVarIBDV (genotype A2d) and OR682618 and OR682619 GenBank accession numbers were obtained. Phylogenetic analysis revealed that both nVarIBDV isolates were closely related to nVarIBDV strains (A2d) circulating in China, exhibiting 100% identity to SD-2020 and 99.5-98.1% similarity to ZD-2018-1, QZ, GX and SG19 strains, respectively. Similarity to USA variant strains, belonging to genotypes A2b (9109), A2c (GLS) and A2a (variant E), respectively, was 95.5-92.6%. Also, the VP2 hypervariable region in those two, A2d, isolates revealed greater similarities to Faragher 52/70 (Vaxxitek®) at 90.4% and to an Indian strain (Ventri-Plus®) and V217 (Xtreme®) at 89.7% and 86-88.9% in other vaccines. Histopathological examination of both the bursa of Fabricius and spleen collected from diseased chickens in flock no. 18 revealed severe atrophy. In conclusion, further studies are required to investigate the epidemiological situation of this novel genotype across the country, and to assess various vaccine protections against nVarIBDV. Additionally, vaccination of breeders with inactivated IBD vaccines including this nVarIBDV is essential to obtain specific maternal antibodies in their broilers.

Сложные вопросы диагностики синдрома неонатальной волчанки

Aim. To describe a clinical case of neonatal lupus with skin syndrome, a retrospective assessment of the significance and genesis of episodes of sinus bradycardia, recorded in utero and persisted postnatally, and neutropenia in the neonatal period. Key points. Neonatal lupus is a rare syndrome characterized by transient dermatitis, various systemic disorders, hematological changes and/ or congenital fetal heart block. At its core, this is a model of a passively acquired transient immune disease of newborns, which is based on the transplacental transfer of specific maternal antibodies represented exclusively by immunoglobulin G through the Fc receptors of the trophoblast. Difficulties for diagnosis represent neonatal lupus cases with minimal clinical manifestations in a newborn from a mother without an established diagnosis of rheumatic disease. Conclusion. In the isolated cutaneous form of neonatal lupus syndrome, specific treatment is not required; observation by a pediatrician with monitoring of a blood test confirming the elimination of maternal antibodies is indicated. However, taking into account the possibility of damage to the conduction system of the heart, registration of a surface electrocardiogram and regular monitoring (at least once every 6 months) of 24-hour electrocardiogram monitoring data are necessary. Keywords: neonatal lupus, newborn, specific antibodies, differential diagnosis.

Protective efficacy of a recombinant enterotoxin antigen in a maternal immunization model and the inhibition of specific maternal antibodies to neonatal oral vaccination

ETEC (enterotoxigenic Escherichia coli) infection is the leading cause of profuse watery diarrhea in mammals, especially among pre-weaning and post-weaning piglets in swine industry. Maternal immunization is a current rational strategy for providing protection to susceptive piglets and reducing the incidence of ETEC-associated diarrhea. Here we evaluated the protective efficiency of a recombinant antigen (MBP-SLS) fused by major enterotoxin subunits (STa-LTB-STb) via a maternal immunization model, and the impacts of maternal antibodies to neonatal oral vaccination were also investigated in the neonates. The high titers of specific IgG and sIgA in pups shown that the maternal antibodies could be transferred passively. Furthermore, the increases of IL-6 and IL-10 cytokines in breast milk and pup serum indicated that immunization on mother could effectively boost the immune system of neonates. Newborn rats from immunized mothers showed a 70% survival rate after ETEC infection. However, the mucosal immune responses of neonates were inhibited by the high level of maternal specific antibodies. Among the oral-vaccinated neonates, born from mock-immunized rats reached the highest survival after ETEC challenge. Collectively, the fusion MBP-SLS antigen could effectively induce strong immune responses in rats during pregnancy and the pups could receive passive protection through specific antibodies transferred via milk and placenta. However, the specific maternal antibodies exhibited an inhibition effect on the mucosal immune responses in offspring.

ACUTE PRIMARY EPSTEIN-BARR VIRUS INFECTION IN 8-MONTH-OLD CHILD: CASE REPORT

This article highlights the difficulties in diagnosis and features of the course of acute primary Epstein-Barr virus infection in an infant. A clinical case of an 8-month-old child with this disease is presented. Primary infection with the Epstein-Barr virus in young children is often characterized by a subclinical course or may be asymptomatic. Peculiarities of acute primary Epstein-Barr virus infection in the child are manifested by purulent-necrotic angina, secondary thrombocytopenia, anaemia of the 1st degree (with minimal changes on the part of the lymph nodes, the absence of hepatosplenomegaly) under the dysfunction of the immune system (age-related immunodeficiency condition). The latter cause and the failure to obtain specific maternal antibodies with breast milk (the child is kept on artificial feeding) have resulted in the severe course of this disease. Immature adaptation mechanisms of the mucous membranes of children lead to the phenomena of dysbiosis in the form of an imbalance of different degrees of severity of the disease. The final diagnosis of the child is based on the isolation of Epstein-Barr virus DNA in the blood serum during the polymerase chain reaction. The child requires dynamic monitoring from a paediatrician and cardiologist that enables to select effective measures to manage the disease and to assess physical development.

Assessment of Anti m-RNA SARS-CoV-2 (BNT162b2) Antibody Titres in Mother and Child Pairs of Breastfeeding Women Vaccinated Post-Delivery.

The global response to the COVID-19 pandemic has been successfully driven by efforts to ramp up access to vaccines. Pregnant or breastfeeding women and their children have not benefited from the vaccines despite their susceptibility to the virus. We investigated whether women who were offered vaccination after delivery passively transferred protective antibodies to their infants via breast milk. Serum was collected from breast feeding mother–infant pairs and analysed for levels of antibodies to the SARS-CoV-2 spike protein using the CLIA chemiluminescence technique. Data were analysed for the significance of the differences using the Mann–Whitney U test and the Spearman’s rank correlation coefficient to determine the strength of the correlation. A total of 13 mothers, mean age 34.86 (95%CI = 33.21–36.48) years and their infants, mean age 15.77 (95%CI = 11.24–20.29) months were enrolled. The mothers had completed their courses of the mRNA BNT162b2 SARS-CoV-2 vaccine during breastfeeding, 8.3 (95%CI = 7.24–9.36) months before the study. All 13 mothers had detectable antibodies to the SARS-CoV-2 spike protein, mean 1252, (95%CI = 736–1769) BAU/mL. Antibodies were detected in 3/13 (23%) breast-fed infants mean 322, (95%CI = 252–897) BAU/mL. There was no correlation between the maternal and infant IgG antibody titres. The time-lag since full vaccination did not correlate to the presence of antibodies in infant sera. Maternal or infant ages did not correlate to the presence of antibodies. Although some children (23%) had anti-SARS-CoV-2 antibodies, there was no association between vaccine-induced COVID-19 spike protein specific maternal IgG antibody titres and the presence of antibodies in the breastfed infants. The data show that the transfer of passive immunity to infants following post-partum vaccination with the mRNA BNT162b2 SARS-CoV-2 vaccine may be infrequent in this population.

Serological Responses to Influenza Vaccination during Pregnancy

Pregnant women, newborns, and infants under six months old are at the highest risk of developing severe and even fatal influenza. This risk is compounded by the inability to vaccinate infants under six months, highlighting the importance of vertically transferred immunity. This review identifies novel insights that have emerged from recent studies using animal models of pregnancy and vaccination. We also discuss the knowledge obtained using existing clinical trials that have evaluated influenza-specific serological responses in pregnant women and how these responses may impact early life immunity. We delineate the mechanisms involved in transferring specific maternal antibodies and discuss the consequences for early life immunity. Most importantly, we highlight the need for continued research using pregnant animal models and the inclusion of pregnant women, a commonly neglected population, when evaluating novel vaccine platforms to better serve and treat communicable diseases.

Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results.

Background: The coronavirus disease 2019 (COVID-19) pandemic has given rise to the need to develop a vaccine as quickly as possible. As pregnant women are at increased risk of contracting severe COVID-19, with higher mortality, it is essential to assess the safety of the vaccines administered during pregnancy. Methods: The aim of this study was to determine the titer of specific maternal and cord antibodies against severe acute respiratory syndrome coronavirus 2 S protein after antenatal vaccination. The secondary objective was to evaluate the ratio of the umbilical cord to the maternal antibody titers. Patients included in the study were enrolled after undergoing voluntary vaccination against COVID-19 during pregnancy at different weeks of gestation. All patients analyzed in our initial study were vaccinated with the BNT162b2 mRNA COVID-19 vaccine. Results: The results of the current study document high anti-S total IgG antibody titers in cord serum at birth in all mother–infant pairs analyzed. The mean umbilical cord blood sample IgG antibody titer anti-S protein was 1026.51 U/mL (±SD 769.25). The mean cord-to-maternal anti–S IgG antibody ratio was 1.28 (±SD 0.798). A significant positive correlation was observed between the week of gestation at which the first dose was administered and the week of gestation at which the second dose was administered, and the respective cord-to-maternal ratio (r = 0.48; p = 0.0029) for the first dose and (r = 0.39; p = 0.0102) for the second dose. Conclusions: To date, despite the prevalence of COVID-19 vaccination, there is a lack of conclusive evidence supporting the safety and efficacy of vaccination of pregnant women. Therefore, the results we present are complementary. Our study suggests that maternal immunization may provide neonatal protection through the transplacental transfer of antibodies. Of particular importance is the demonstration that antibody transfer is correlated with the time from vaccination to delivery, which may allow future determination of the optimal timing of COVID-19 vaccination in pregnant women.

A Protein Subunit Filovirus Vaccine Facilitates Maternal Immunization in Mice

Abstract Ebola virus disease (EVD) is highly pathogenic and virulent and has caused large scale outbreaks in Central and West Africa. To date there are no known correlates of protection however, recently the FDA and EMA have approved a vaccine, Ervebo. This vaccine utilizes a replication competent viral vector which may be contraindicated in immunocompromised individuals, pregnant women, and infants. Our lab has developed a recombinant protein subunit vaccine, a platform that is generally considered safe for immunocompromised, pregnant women, and infants. Our vaccine, when properly adjuvanted, demonstrates protection in non-human primates and may also induce maternal immunization. Maternal Immunization is the phenomena of inducing passive immunity via maternal antibody. This occurs via transfer of IgG using the FcRn. This receptor binds the Fc portion of IgG in a pH dependent manner which facilitates transcytosis of IgG across the placental, mammary tissue, as well as gut epithelial layer. In rodents, maternal IgG is transferred across the gut epithelia throughout the nursing period. This project demonstrates in mice the immunogenicity of a protein subunit vaccine comprised of Ebola glycoprotein and adjuvant administered during gestation as well as the transfer of antigen specific maternal antibody to offspring through milk. To investigate maternal immunization we vaccinated female Swiss Webster mice during gestation and measured antigen specific IgG levels in both the mothers and pups as well as in the milk. Antigen specific maternal antibody titers found in pup sera mimic those found in fully immunized adult females weeks after weaning, indicating the potential for maintaining an antigen specific humoral response in neonates.

Vertically Transferred Immunity in Neonates: Mothers, Mechanisms and Mediators.

Over the last years, an increasing number of outbreaks of vaccine-preventable infectious diseases has been reported. Besides elderly and immunocompromised individuals, newborns and small infants are most susceptible to infections, as their immune system is still immature. This vulnerability during infancy can be mitigated by the transplacental transfer of pathogen-specific antibodies and other mediators of immunity from mother to the fetus during pregnancy, followed postnatally by breast milk-derived immunity. Since this largely antibody-mediated passive immunity can prevent the newborn from infections, neonatal immunity depends strongly on the maternal concentration of respective specific antibodies during pregnancy. If titers are low or wane rapidly after birth, the protection transferred to the child may not be sufficient to prevent disease. Moreover, emerging concepts propose that mothers may transfer active immunity to the newborns via vertical transfer of pathogen-specific T cells. Overall, a promising strategy to augment and prolong neonatal immunity is to vaccinate the mother before or during pregnancy in order to boost maternal antibody concentrations or availability of specific T cells. Hence, a large number of pre-and postconceptional vaccine trials have been carried out to test and confirm this concept. We here highlight novel insights arising from recent research endeavors on the influence of prenatal maternal vaccination against pathogens that can pose a threat for newborns, such as measles, pertussis, rubella and influenza A. We delineate pathways involved in the transfer of specific maternal antibodies. We also discuss the consequences for children’s health and long-term immunity resulting from an adjustment of prenatal vaccination regimes.

Rotavirus specific maternal antibodies and immune response to RV3-BB rotavirus vaccine in central java and yogyakarta, Indonesia

BackgroundPlacental or breast milk maternal antibodies can potentially reduce oral rotavirus vaccine efficacy in developing countries. We aimed to examine the relationship between the level of rotavirus specific immunoglobulin A (IgA) and neutralising antibodies (NA) in colostrum and breast milk and cord IgG, with cumulative vaccine take following one and three doses of oral RV3-BB rotavirus vaccine within a Phase IIb trial in Indonesia. Methods196 infants received three doses of RV3-BB in a randomized, double-blinded trial, using a neonatal schedule (first dose at 0–5 days of age, n = 61), an infant schedule (first dose at ~ 8 weeks of age, n = 67) or placebo (n = 68). Rotavirus specific IgA and NA in colostrum and breast milk, rotavirus specific cord IgG, Serum IgA and stool excretion were measured. ResultsThere was little evidence of an association between IgA in colostrum or breast milk and cumulative vaccine take after three doses in the neonatal or infant groups. In the neonatal group, there was a negative association between IgG titre in cord blood and cumulative vaccine take (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.92–1.00; p = 0.03) and serum IgA response (OR 0.94; 95%CI 0.89–0.99; p = 0.02) after one dose of vaccine, which were not evident after three doses in the neonatal or infant groups. ConclusionsAmongst Indonesian infants we did not find an association between IgA in colostrum or breast milk and vaccine take after 3 doses of RV3-BB vaccine. Maternal rotavirus antibodies in breast milk appear to have minimal impact on RV3-BB vaccine take when administered with a short delay in breast-feeding in settings with a high rotavirus disease burden.

Interaction between maternally derived antibodies and heterogeneity in exposure combined to determine time-to-first Plasmodium falciparum infection in Kenyan infants

BackgroundStudies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate. This can occur because high malaria exposure may drive high antibody responses, leading to an apparent positive association between immune response and infection rate. The neonatal period provides a unique window to study the protective effects of antibodies, because waning maternally-derived antibodies lead to different levels of protection with time.MethodsThis study uses data from two well-defined infant cohorts in Western Kenya with different burdens of malaria transmission. Survival models were used to assess how the magnitude of maternally derived malaria-specific IgG antibody (to 24 malaria antigens measured using Luminex beads) affected the time-to-first Plasmodium falciparum infection (detected by PCR). In addition, mathematical models were used to assess how the frequency of malaria infection varied between the cohorts with different exposure levels.ResultsDespite differences in underlying malaria incidence in the two regions, there was no difference in time-to-first malaria infection between the cohorts. However, there was a significant period of protection observed in children with high initial MSP1 (42 kDa fragment)-specific antibody levels, but this protection was not observed in children with low antibody levels. Children from the high transmission cohort had both longer initial periods of protection from malaria (attributable to higher initial antibody levels), but more rapid time-to-first-infection once malaria specific maternal antibodies declined below protective levels (attributable to higher exposure rates).ConclusionThis study demonstrates the complex interaction between passive (maternally-derived) immunity and the degree of malaria exposure in infants. Children from regions of high malaria transmission had higher levels of maternally-derived antibodies in early life, which led to a significant protection for several months. However, once this immunity waned, the underlying higher frequency of infection was revealed. A better understanding of the interaction between malaria exposure, immunity, and transmission risk will assist in identifying protective immune responses in P. falciparum infection.

Exposure of yellow-legged gulls to Toxoplasma gondii along the Western Mediterranean coasts: Tales from a sentinel.

Efficiently tracking and anticipating the dynamics of infectious agents in wild populations requires the gathering of large numbers of samples, if possible at several locations and points in time, which can be a challenge for some species. Testing for the presence of specific maternal antibodies in egg yolks sampled on the colonies could represent an efficient way to quantify the exposure of breeding females to infectious agents, particularly when using an abundant and widespread species, such as the yellow-legged gull (Larus michahellis). We used such an approach to explore spatio-temporal patterns of exposure to Toxoplasma gondii, a pathogenic protozoan responsible of toxoplasmosis in humans and other warm-blooded vertebrates. First, we tested the validity of this approach by exploring the repeatability of the detection of specific antibodies at the egg level using two different immunoassays and at the clutch level using an occupancy model. Then, samples gathered in 15 colonies from France, Spain and Tunisia were analysed using an immunoassay detecting antibodies specifically directed against T. gondii. Prevalence of specific antibodies in eggs was overall high while varying significantly among colonies. These results revealed that T. gondii circulated at a large spatial scale in the western Mediterranean yellow-legged gull population, highlighting its potential role in the maintenance community of this parasite. Additionally, this study illustrates how species commensal to human populations like large gulls can be used as wildlife sentinels for the tracking of infectious agents at the human-wildlife interface, notably by sampling eggs.

Congenital chicken pox: a clinical case of a child at the age of 6 days

Chicken pox can be both acquired and congenital. The information is presented in the form of a diagram on the incidence of chickenpox in St. Petersburg, which shows that among children, the most common are children aged 3 to 6 years. A brief etiology of the varicella virus, a clinical picture, describing the typical and atypical forms of the disease. Due to the airborne pathway and the high infectivity of the infection, there is a risk of contracting seronegative pregnant women, which is 50%. It has been established that for 1,000 deliveries there are from 1 to 5 cases of chicken pox. In addition, the flow of chicken pox and lethality depends on the possibility of transmitting from mother to child protective specific maternal antibodies. Features of infection in pregnant women and fetus, the severity of intrauterine infection, depending on the timing of infection are described. The characteristics of varicella and neonatal chickenpox syndrome, as well as nonspecific clinical manifestations of the infectious process in the newborn are presented. We describe our own clinical observation of congenital varicella in a 6-day-old child, born from a mother who fell ill four days before the birth. The inclusion in the complex therapy of children with congenital chickenpox recombinant interferon-α2β with antioxidants (viferon rectal suppositories) contributes to the rapid positive dynamics of clinical symptoms, easier flow, prevents the layering of acute respiratory infections, reduces the material costs of treatment.

Maternal Humoral Immune Correlates of Peripartum Transmission of Clade C HIV-1 in the Setting of Peripartum Antiretrovirals.

Despite the widespread use of antiretrovirals (ARV), more than 150,000 pediatric HIV-1 infections continue to occur annually. Supplemental strategies are necessary to eliminate pediatric HIV infections. We previously reported that maternal HIV envelope-specific anti-V3 IgG and CD4 binding site-directed antibodies, as well as tier 1 virus neutralization, predicted a reduced risk of mother-to-child transmission (MTCT) of HIV-1 in the pre-ARV era U.S.-based Women and Infants Transmission Study (WITS) cohort. As the majority of ongoing pediatric HIV infections occur in sub-Saharan Africa, we sought to determine if the same maternal humoral immune correlates predicted MTCT in a subset of the Malawian Breastfeeding, Antiretrovirals, and Nutrition (BAN) cohort of HIV-infected mothers (n = 88, with 45 transmitting and 43 nontransmitting). Women and infants received ARV at delivery; thus, the majority of MTCT was in utero (91%). In a multivariable logistic regression model, neither maternal anti-V3 IgG nor clade C tier 1 virus neutralization was associated with MTCT. Unexpectedly, maternal CD4 binding-site antibodies and anti-variable loop 1 and 2 (V1V2) IgG were associated with increased MTCT, independent of maternal viral load. Neither infant envelope (Env)-specific IgG levels nor maternal IgG transplacental transfer efficiency was associated with transmission. Distinct humoral immune correlates of MTCT in the BAN and WITS cohorts could be due to differences between transmission modes, virus clades, or maternal antiretroviral use. The association between specific maternal antibody responses and in utero transmission, which is distinct from potentially protective maternal antibodies in the WITS cohort, underlines the importance of investigating additional cohorts with well-defined transmission modes to understand the role of antibodies during HIV-1 MTCT.

Defining the vaccination window for respiratory syncytial virus (RSV) using age-seroprevalence data for children in Kilifi, Kenya.

BackgroundRespiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in early life and a target for vaccine prevention. Data on the age-prevalence of RSV specific antibodies will inform on optimizing vaccine delivery.MethodsArchived plasma samples were randomly selected within age strata from 960 children less than 145 months of age admitted to Kilifi County Hospital pediatric wards between 2007 and 2010. Samples were tested for antibodies to RSV using crude virus IgG ELISA. Seroprevalence (and 95% confidence intervals) was estimated as the proportion of children with specific antibodies above a defined cut-off level. Nested catalytic models were used to explore different assumptions on antibody dynamics and estimate the rates of decay of RSV specific maternal antibody and acquisition of infection with age, and the average age of infection.ResultsRSV specific antibody prevalence was 100% at age 0-<1month, declining rapidly over the first 6 months of life, followed by an increase in the second half of the first year of life and beyond. Seroprevalence was lowest throughout the age range 5–11 months; all children were seropositive beyond 3 years of age. The best fit model to the data yielded estimates for the rate of infection of 0.78/person/year (95% CI 0.65–0.97) and 1.69/person/year (95% CI 1.27–2.04) for ages 0-<1 year and 1-<12 years, respectively. The rate of loss of maternal antibodies was estimated as 2.54/year (95% CI 2.30–2.90), i.e. mean duration 4.7 months. The mean age at primary infection was estimated at 15 months (95% CI 13–18).ConclusionsThe rate of decay of maternal antibody prevalence and subsequent age-acquisition of infection are rapid, and the average age at primary infection early. The vaccination window is narrow, and suggests optimal targeting of vaccine to infants 5 months and above to achieve high seroconversion.

A Neonatal Murine Model of Coxsackievirus A6 Infection for Evaluation of Antiviral and Vaccine Efficacy.

Hand, foot, and mouth disease (HFMD) is a global health concern. Family Picornaviridae members, particularly enterovirus A71 (EVA71) and coxsackievirus A16 (CVA16), are the primary etiological agents of HFMD; however, a third enterovirus A species, CVA6, has been recently associated with epidemic outbreaks. Study of the pathogenesis of CVA6 infection and development of antivirals and vaccines are hindered by a lack of appropriate animal models. We have developed and characterized a murine model of CVA6 infection that was employed to evaluate the antiviral activities of different drugs and the protective efficacies of CVA6-inactivated vaccines. Neonatal mice were susceptible to CVA6 infection via intramuscular inoculation, and the susceptibility of mice to CVA6 infection was age and dose dependent. Five-day-old mice infected with 105.5 50% tissue culture infective doses of the CVA6 WF057R strain consistently exhibited clinical signs, including reduced mobility, lower weight gain, and quadriplegia with significant pathology in the brain, hind limb skeletal muscles, and lungs of the infected mice in the moribund state. Immunohistochemical analysis and quantitative reverse transcription-PCR (qRT-PCR) analyses showed high viral loads (11 log10/mg) in skeletal muscle, and elevated levels of interleukin-6 (IL-6; >2,000 pg/ml) were associated with severe viral pneumonia and encephalitis. Ribavirin and gamma interferon administered prophylactically diminished CVA6-associated pathology in vivo, and treatment with IL-6 accelerated the death of neonatal mice. Both specific anti-CVA6 serum and maternal antibody play important roles in controlling CVA6 infection and viral replication. Collectively, these findings indicate that this neonatal murine model will be invaluable in future studies to develop CVA6-specific antivirals and vaccines.IMPORTANCE Although coxsackievirus A6 (CVA6) infections are commonly mild and self-limiting, a small proportion of children may have serious complications, such as encephalitis, acute flaccid paralysis, and neurorespiratory syndrome, leading to fatalities. We have established a mouse model of CVA6 infection by inoculation of neonatal mice with a CVA6 clinical isolate that produced consistent pathological outcomes. Here, using this model of CVA6 infection, we found that high levels of IL-6 were associated with severe viral pneumonia and encephalitis, as in an evaluation of antiviral efficacy in vivo, IL-6 had no protective effect and instead accelerated death in neonatal mice. We demonstrated that, as antiviral drugs, both gamma interferon and ribavirin played important protective roles in the early stages of infection, with increased survival in treated neonatal mice challenged with CVA6. Moreover, active and passive immunization with the inactivated vaccines and anti-CVA6 serum also protected mice against homologous challenge infections.

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

ABSTRACTBackground: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident.Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression.Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05).Conclusions: The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or stool excretion following 3 doses of RV3-BB Rotavirus Vaccine administered using either a neonatal or infant schedule in New Zealand infants.

Food availability modulates the effects of maternal antibodies on growth and immunity in young feral pigeons

It is now widely acknowledged that mothers can transfer their own immune experience to their progeny through the allocation of specific maternal antibodies (hereafter referred as MatAb) that can shape offspring phenotype and affect their fitness. However, the importance of environmental variability in modulating the effects of MatAb on offspring traits is still elusive. Using an experimental approach, we investigated how food availability interacted with MatAb to solve the trade‐off between humoral immunity and growth in young feral pigeons Columba livia. Results show that the inhibitory effect of MatAb on the humoral response of chicks was detected regardless of the food treatment. In addition, body mass growth was higher in chicks receiving lower amounts of maternal antibodies but only in chicks of the ad libitum food treatment. This contradicts previous studies and suggests that the transfer of MatAb could entail some costs for chicks and reduce their growth. Taken together these results reinforce the idea that the maternal antibodies play a central role in shaping offspring life‐history traits but that their adaptive value is highly dependent on the environmental context in which they are transmitted by the mother.

Induction of non-specific suppression in chicks by specific combination of maternal antibody and related antigen.

Specific immune suppression in newly hatched chicks induced by specific maternal antibodies has been reported. Laying hens were immunized with dinitrophenyl-keyhole limpet hemocyanin (DNP-KLH). Purified maternal anti-DNP and non-specific immunoglobulin (Ig) Y antibodies were transferred by yolk sac inoculation to newly hatched chicks, and then, they were immunized with an optimum immunogenic dose of DNP-KLH at 1 and 4 weeks of age. Concentrations of anti-DNP antibodies in serum samples of these chicks were measured by using Enzyme-linked immunosorbent assay (ELISA). Proportions of T-cell subsets in peripheral blood of these chicks were also measured by flow cytometric analysis at 5 weeks of age (one week after the second immunization). Suppression of anti-DNP antibody response and down-regulation of CD3+CD4+ cells were observed in the chicks received high dose of maternal anti-DNP antibodies and immunized with DNP-KLH. On the other hand, normal anti-DNP antibody response and normal proportion of CD3+CD4+ cells were observed in the chicks received high dose of non-specific IgY antibodies and immunized with DNP-KLH. Furthermore, when chicks received high dose of maternal anti-DNP antibodies and immunized with DNP-KLH at 1 and 4 weeks of age and then with rabbit serum albumin (RSA) at 5 and 8 weeks of age, their primary anti-RSA response was also significantly suppressed. We indicate here that specific maternal antibodies can affect both B and T cell responses and induce non-specific suppression against different antigens. However, this non-specific suppression does not continue for a long time.

ROLE OF PREEXISTING VIRUS-SPECIFIC IgG IN PRIMARY DISEASE AND IN REINFECTION WITH RESPIRATORY SYNCYTIAL VIRUS

Abstract. The aim of the study is evaluation of links between presence in blood of specific pre-existing IgG to respiratory-syncytial virus (RSV), clinical course of RSV infection and character specific to RSV humoral immune response in patients of different ages. The antibodies were detected by ELISA using whole RS virus or synthetic peptides corresponded to the selected determinants of the envelope RSV proteins. It was shown that RS specific maternal IgG antibodies passively transferred to babies in utero can circulate in the blood up to 10 months of life. The analysis of paired sera of 45 babies in the age of 1–10 months revealed firstly that presence of maternal IgG specific antibodies to the conservative B-cell immunogenic determinants of the F-protein (amino acids 221–232) and/or the G-protein (amino acids 152–164 and 184–198) is coupled with more high morbidity of primary RSV infection (89% versus 56%, p = 0.023), and also with more high frequency of complicated by bronchus obstruction course of the disease (81% versus 20%, р = 0.001) in compare with babies who were serologically negative to the maternal determinants specific antibodies. The correlation analysis has shown that the high presence of maternal determinant-specific IgG in the blood in babies till 10 months of life is associated in the case of primary infection with disbalance of humoral anti-viral immune response: intensive synthesis of serum RSV IgA. This is evidence of complicated course of infection with simultaneous suppression of response to RSV specific IgG. As opposed to the primary RSV infection in patients older than 3 years (n = 121) it was not detected links between anamnestic determinant-specific IgG synthesized by own immune system as the results of previous disease episodes and synthesis of anti-RSV IgG, IgM, IgE and IgA in RSV re-infections. In the contrast to babies in more older patients the feedback connection between level of pre-existing determinant-specific “memory IgG” and diagnostics of RSV infection has been established.