Passive Transfer Of Antibodies Research Articles

Evaluation of longitudinal passive immunity transfer against lumpy skin disease virus in calves by different serological methods.

To implement effective lumpy skin disease (LSD) control measures, such as timely vaccination, particularly in calves and serological monitoring, it is necessary to evaluate immune response after vaccination, both in adult cattle and in their calves. The aim of this study was to evaluate passive immunity transfer and duration of maternal antibodies against lumpy skin disease virus (LSDV) in calves born to vaccinated cows by two different serological methods. The longitudinal study was carried out on two farms in Serbia where no cases were reported during LSD outbreak in 2016. Fifteen cows on each farm were vaccinated and revaccinated with attenuated vaccine - Neethling strain. A total of 30 cows and 30 calves on both farms were included in the study. Serum samples from cows were collected on calving day and serum samples from their respective calves on days 10, 20, 30, 45, 60, 75, 90, 105 and 120 after birth. Colostrum samples were collected only from 15 cows on one farm. In order to determine the presence of antibodies against LSDV a total of 30 cow sera samples, 15 colostrum samples and 270 calf sera samples were examined by commercial enzyme-linked immunosorbent assay (ELISA) and modified virus neutralization test (VNT). Overall, the performance of both serological tests was very satisfactory. The results of this longitudinal study showed that persistence of passive immunity in calves is less than 4 months, and that most calves are not protected against LSDV at that age. Since the vaccination is the most important control measure against LSDV, the recommended age of six months for vaccination of calves born to vaccinated cows should be reassessed to achieve the most optimal protection against LSD.

Immune response induced by a Streptococcus suis multi-serotype autogenous vaccine used in sows to protect post-weaned piglets

Streptococcus suis is a bacterial pathogen that causes important economic losses to the swine industry worldwide. Since there are no current commercial vaccines, the use of autogenous vaccines applied to gilts/sows to enhance transfer of passive immunity is an attractive alternative to protect weaned piglets. However, there is no universal standardization in the production of autogenous vaccines and the vaccine formulation may be highly different among licenced manufacturing laboratories. In the present study, an autogenous vaccine that included S. suis serotypes 2, 1/2, 5, 7 and 14 was prepared by a licensed laboratory and administrated to gilts using a three-dose program prior to farrowing. The antibody response in gilts as well as the passive transfer of antibodies to piglets was then evaluated. In divergence with previously published data with an autogenous vaccine produced by a different company, the increased response seen in gilts was sufficient to improve maternal antibody transfer to piglets up to 5 weeks of age. However, piglets would still remain susceptible to S. suis disease which often appears during the second part of the nursery period. Vaccination did not affect the shedding of S. suis (as well as that of the specific S. suis serotypes included in the vaccine) by either gilts or piglets. Although all antibiotic treatments were absent during the trial, the clinical protective effect of the vaccination program with the autogenous vaccine could not be evaluated, since limited S. suis cases were present during the trial, confirming the need for a complete evaluation of the clinical protection that must include laboratory confirmation of the aetiological agent involved in the presence of S. suis-associated clinical signs. Further studies to evaluate the usefulness of gilt/sow vaccination with autogenous vaccines to protect nursery piglets should be done.

Mechanisms of autoimmune encephalitis.

To provide an overview of the pathogenic mechanisms involved in autoimmune encephalitides mediated by antibodies against neuronal surface antigens, with a focus on NMDAR and LGI1 encephalitis. In antibody-mediated encephalitides, binding of IgG antibodies to neuronal surface antigens results in different pathogenic effects depending on the type of antibody, IgG subclass and epitope specificity. NMDAR IgG1 antibodies cause crosslinking and internalization of the target, synaptic and brain circuitry alterations, as well as alterations of NMDAR expressing oligodendrocytes, suggesting a link with white matter lesions observed in MRI studies. LGI1 IgG4 antibodies, instead, induce neuronal dysfunction by disrupting the interaction with cognate proteins and altering AMPAR-mediated signaling. In-vitro findings have been corroborated by memory and behavioral changes in animal models obtained by passive transfer of patients' antibodies or active immunization. These models have been fundamental to identify targets for innovative therapeutic strategies, aimed at counteracting or preventing antibody effects, such as the use of soluble ephrin-B2, NMDAR modulators (e.g., pregnenolone, SGE-301) or chimeric autoantibody receptor T cells (CAART) in models of NMDAR encephalitis. A deep understanding of the pathogenic mechanisms underlying antibody-mediated encephalitides is crucial for the development of new therapeutic approaches targeting brain autoimmunity.

Acetylcholine Binding Receptor Positivity from Passive Antibody Transfer in a Case of Progressive Muscular Atrophy (P11-11.009)

Acetylcholine Binding Receptor Positivity from Passive Antibody Transfer in a Case of Progressive Muscular Atrophy (P11-11.009)

Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder. Multiple genetic and environmental factors leading to progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SN) and consequent depletion of dopamine were described. Current clinical approaches, such as dopamine replacement or deep brain stimulation using surgically implanted probes, provide symptomatic relief but cannot modify disease progression. Therefore, disease-modifying therapeutic tools are urgently needed. Immunotherapy approaches, including passive transfer of protective antibodies and their fragments, have shown therapeutic efficacy in several animal models of neurodegenerative diseases, including PD. Recombinant antibody fragments are promising alternatives to conventional full-length antibodies. Modern computational approaches and molecular biology tools, directed evolution methodology, and the design of tissue-penetrating fusion peptides allowed for the development of recombinant antibody fragments with superior specificity and affinity, reduced immunogenicity, the capacity to target hidden epitopes and cross the blood-brain barrier (BBB), higher solubility and stability, the ability to refold after heat denaturation, and inexpensive large-scale production. In addition, antibody fragments do not induce microglia Fcγ receptor (FcγR)-mediated proinflammatory response and tissue damage in the central nervous system (CNS), because they lack the Fc portion of the immunoglobulin molecule. In the present review, we summarized data on recombinant antibody fragments evaluated as immunotherapeutics in preclinical models of PD and discussed their potential for developing therapeutic and preventive protocols for patients with PD.

VEDOLIZUMAB DOES NOT ALTER IMMUNOGLOBULIN LEVELS IN BREASTMILK OF MOTHERS WITH IBD

Abstract Diarrheal diseases are a major cause of infant mortality worldwide. Breastfeeding helps prevent such diseases by passive transfer of maternal antibodies against gastrointestinal pathogens previously encountered by the mother. The antibody secreting cells (ASC) that populate the lactating mammary gland (LMG) are educated in gastrointestinal lymphoid tissues, thus they express integrin a4b7. To recruit these ASC, the LMG expresses MAdCAM-1 and CCL28. Vedolizumab (vedo) blocks a combinatorial epitope on integrin a4b7, interfering with lymphocyte recruitment to the gut. Given the shared homing determinants between the gut and LMG, we investigated whether vedo might interfere with ASC trafficking to the LMG, therefore decreasing immunoglobulin (Ig) levels in breast milk. We measured Ig levels by ELISA in cryopreserved breast milk from mothers enrolled in Mommy’s Milk biorepository at the University of California, San Diego without and with Ulcerative Colitis(UC) or Crohn’s Disease(CD) and lactating mothers with UC and CD treated with vedo for more than 18 months. Milk samples were collected between 1 month and 15.45 months after childbirth. The levels of secretory IgA (SIgA) in breast milk of mothers without IBD (n=45) was not different from those of mothers with CD not on vedo (n=15) (301 ± 147 ug/mL vs. 322 ± 207 ug/mL). However, milk SIgA from mothers with UC not on vedo (n=7) were lower than non-IBD controls (213 ± 149 ug/mL vs. 301 ± 147ug/mL, p<0.01). We then compared milk SIgA from patients with CD and UC treated with vedo (CD: n= 9; 256 ± 80ug/mL, UC: n=10; 283 ± 87 ug/mL) with those from non-IBD controls (n=45; 301 ± 147ug/mL) and found no differences. Similarly, SIgA levels were not different between CD with or without vedo (256 ± 80 ug/mL vs. 322 ± 207 ug/mL) and as compared with non-IBD controls SIgA in patients with UC with vedo were unexpectedly higher than UC without vedo (283 ±87 ug/mL vs 213 ± 149 ug/mL, p<0.05). The levels of secretory IgM (SIgM) in milk were not different between mothers with UC or CD treated with vedo compared with non-IBD controls (65 ± 34 ug/mL, 69 ± 32 ug/mL, and 56 ± 37 ug/mL, respectively). Similarly, no significant difference was seen between patients with UC or CD not treated with vedo compared with the non-IBD controls (58±26 ug/mL, and 46 ± 24 ug/mL respectively). We conclude that vedo does not reduce SIgA nor SIgM levels in lactating mothers with IBD. We speculate that the higher SIgA in patients with UC treated with vedo is due to the small sample size. Vedo does not interfere with passive immunity during the lactation period, thus ASC must be able to use another integrin to arrest on microvessels of the LMG during the final stages of pregnancy.

Immunotherapy against tau pathology in mouse models requires cytosolic Fc receptor TRIM21

AbstractBackgroundThe passive transfer of monoclonal antibodies reduces tau pathology in mouse models and is under evaluation as a potential immunotherapeutic strategy against Alzheimer’s disease and other tauopathies. The mechanisms that drive therapeutic protection of anti‐tau antibodies are not well understood.MethodP301S tau transgenic animals were treated with antibodies against pS422 and analysed for tau pathology by biochemical fractionation. Organotypic hippocampal slice cultures were used as a model of tau seeding and neutralisation. AAV serotypes were used to deliver tau‐selective degraders.ResultGenetic deletion of the cytosolic antibody receptor and E3 ubiquitin ligase TRIM21 rendered tau immunotherapy ineffective in animal models. In organotypic slices, expression of TRIM21 was essential for protection against seeded aggregation of tau. Cytosolic antibody‐tau complexes were visible inside neurons in complex with TRIM21 shortly after application of tau assemblies and antibodies to the cell exterior. Nanobody‐based degraders were developed using TRIM21 and found to protect against tau pathology.ConclusionAnti‐tau antibodies can engage extracellular tau seeds and enter neurons as a complex. Following cytosolic entry, TRIM21 engages the antibodies and mediates neutralisation of tau seeding activity. The results reveal a mechanism that can be optimised for future immunotherapeutics. In this direction, AAV‐delivered degraders reveal a route by which tau aggregates may be selectively removed from the brain.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection

Pregnancy is associated with a higher risk of adverse symptoms and outcomes for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection for both mother and neonate. Antibodies can provide protection against SARS-CoV-2 infection and are induced in pregnant women after vaccination or infection. Passive transfer of these antibodies from mother to fetus in utero may provide protection to the neonate against infection. However, it is unclear whether the magnitude or quality and kinetics of maternally derived fetal antibodies differs in the context of maternal infection or vaccination. We aimed to determine whether antibodies transferred from maternal to fetus differed in quality or quantity between infection- or vaccination-induced humoral immune responses. We evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from New Orleans, Louisiana, with histories of SARS-CoV-2 infection and/or vaccination. Plasma was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. Responses were compared between 4 groups according to maternal infection and vaccination. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies compared to naive subjects. Vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.

Investigation of Anti-SARS-CoV-2-specific IgG Levels in Breast Milk after Vaccination or COVID-19 Infection.

Newborns are vulnerable to all types of infections due to their developing immune system. To compensate for their immune immaturity, newborns rely on the passive transfer of antibodies through the placenta and own mother's breast milk (BM). In the present study, we investigated whether vaccination against SARS-CoV-2 leads to the presence of antibodies in BM. Furthermore, we compared the levels of SARS-CoV-2-specific anti-spike (anti-S) IgG antibodies in the BM of mothers who were vaccinated against Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or had coronavirus disease 2019 (COVID-19) infection naturally or were vaccinated after natural infection. This was a prospective cohort study conducted in the Ondokuz Mayis University Faculty of Medicine. Forty-six mothers who had at least two doses of the BNT162b2 messenger RNA-based vaccine and/or had a history of symptomatic COVID-19 infection were included in the study. BM samples were analyzed by the Abbott Architect SARS-CoV-2 IgG II Quant kit following the manufacturer's instructions. Forty-six mothers with an average age of 29.7 ± 5.7 years participated the study: 18 (39.1%) had COVID-19 infection + BTN162b2 vaccine, 17 (37.0%) had BTN162b2 vaccine, and 11 (23.9%) had natural infection. The highest SARS-CoV-2-specific anti-S IgG antibody titers in BM were found in mothers who were vaccinated following the infection (anti-SARS-CoV-2 IgG: 32.48 ± 57.1 arbitrary units AU/mL). However, no significant difference in anti-SARS-CoV-2 antibody levels was observed between the three groups (p = 0.641). No antibody was detected in 15.2% of BM samples. Both vaccination and natural COVID-19 infection during pregnancy leads to the passive transfer of specific anti-SARS-CoV-2 IgG antibodies to BM. These results are important to overcome vaccine hesitancy and increase vaccination levels in expectant mothers. · We investigated the levels of SARS-CoV-2 antibodies in BM after natural infection and vaccination.. · Anti-SARS-CoV-2 IgG antibodies were detected in 39 (84.8%) BM samples.. · The highest titers in BM were found in mothers who were vaccinated following natural infection..

Recombinant Antibody Fragments for Neurological Disorders: An Update.

Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in pre-clinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer ́s disease(AD), Parkinson ́s disease (PD), frontotemporal dementia (FTD), Huntington ́s disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.

When does humoral memory enhance infection?

Antibodies and humoral memory are key components of the adaptive immune system. We consider and computationally model mechanisms by which humoral memory present at baseline might increase rather than decrease infection load; we refer to this effect as EI-HM (enhancement of infection by humoral memory). We first consider antibody dependent enhancement (ADE) in which antibody enhances the growth of the pathogen, typically a virus, and typically at intermediate 'Goldilocks' levels of antibody. Our ADE model reproduces ADE in vitro and enhancement of infection in vivo from passive antibody transfer. But notably the simplest implementation of our ADE model never results in EI-HM. Adding complexity, by making the cross-reactive antibody much less neutralizing than the de novo generated antibody or by including a sufficiently strong non-antibody immune response, allows for ADE-mediated EI-HM. We next consider the possibility that cross-reactive memory causes EI-HM by crowding out a possibly superior de novo immune response. We show that, even without ADE, EI-HM can occur when the cross-reactive response is both less potent and 'directly' (i.e. independently of infection load) suppressive with regard to the de novo response. In this case adding a non-antibody immune response to our computational model greatly reduces or completely eliminates EI-HM, which suggests that 'crowding out' is unlikely to cause substantial EI-HM. Hence, our results provide examples in which simple models give qualitatively opposite results compared to models with plausible complexity. Our results may be helpful in interpreting and reconciling disparate experimental findings, especially from dengue, and for vaccination.

A narrative review of COVID-19 vaccination in pregnancy and breastfeeding.

The Coronavirus pandemic has affected millions of people due to the spread of the Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) virus. Pregnant individuals and infants are most vulnerable given the increased risk of developing severe complications from SARS-CoV-2 infection. Recently, COVID-19 vaccination is recommended for pregnant women and infants starting at 6 months of age to prevent disease contraction and minimize disease severity. We conducted a review of the literature on COVID-19 vaccination to discuss vaccine safety and efficacy, immunity after maternal vaccination, transplacental transfer and persistence of antibodies, and public health implications. Current evidence supports the safety and efficacy of vaccination during pregnancy. Maternal vaccination provides greater antibody persistence in infants compared to immunity from natural infection. Furthermore, vaccination has demonstrated an increased rate of passive antibody transfer through the placenta and breast milk. Public health interventions are important in achieving herd immunity and ultimately ending the pandemic. IMPACT: This article highlights the benefits of COVID-19 vaccination during pregnancy with a review of the data describing safety and efficacy, passive and active immunity after maternal immunization, trans-placental transfer and persistence of protective antibodies, and public health implications. With this information, healthcare providers can provide up-to-date knowledge to their pregnant patients to help them form an informed decision on vaccination and combat vaccine hesitancy.

Hyperimmune Globulins for the Management of Infectious Diseases

This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.

Passive Transfer of Animal-Derived Polyclonal Hyperimmune Antibodies Provides Protection of Mice from Lethal Lassa Virus Infection.

Lassa virus (LASV) can cause severe acute systemic infection in humans. No approved antiviral drugs or vaccines are currently available. Antibody-based therapeutics are considered a promising treatment strategy in the management of LASV disease. We used chimeric Ifnar-/- C57BL/6 (Ifnar-/- Bl6) mice, a lethal LASV mouse model, to evaluate the protective efficacy of polyclonal antibodies purified from sera of rabbits hyperimmunized with virus-like particles displaying native-like LASV glycoprotein GP spikes. Polyclonal anti-LASV GP antibodies provided 100% protection against lethal LASV infection in a pre- and post-exposure treatment setting and prevented LASV disease. Treatment also significantly lowered viremia level and virus load in organs. When treatment was initiated at the onset of symptoms, the hyperimmune antibodies provided partial protection and increased the survival rate by 80%. Our findings support the consideration of animal-derived hyperimmune antibodies targeting GP as an effective treatment option for highly pathogenic LASV.

Role of antibody screening in high titre group O donors

Red Cells, Fresh Frozen Plasma (FFP) and Platelets (RDP/SDP) prepared from donors with group O may have high titers of anti-A, anti-B and/or anti-A,B antibodies. When such components given to non-group O patients, this high titre can result in haemolytic transfusion reactions (HTRs). Such group O donors are generally termed ‘high-titer group O donors. Significant amounts of ABO antigen being present on the platelet surface and anti-ABO iso-agglutinins being present in the donor’s plasma, Platelet transfusions need to take into account the issues. Although relatively rare, but acute intravascular haemolytic transfusion reaction has been caused by passive transfer of anti-A and anti-B antibodies, present in group O donors. This study aimed to identify the prevalence of high titre antibodies in group O donors. Thus, titre are performed in randomly selected group O donors from different gender and age group to identify best available source of products for Platelet and follow up transfusions.: Randomly selected 100 O blood group donors were included in the study. Samples from these donors were tested for ABO antibody (both IgM and IgG) titres using conventional tube technique at RT and 37°C at Indirect Antiglobulin phase. Statistical analysis was performed using two sample t-test and anova test.Donors included in the present study were mainly male (85%) donors. ABO antibody titres ranged from 0 to 2048. In the present study, Anti-B (IgG) titer is significantly higher than other antibodies in both genders.There are a large proportion of group O donors having high titres of antibodies and hence a routine pretransfusion screening for such antibodies can prevent the development of hemolytic transfusion reaction by issuing only low titre components for out of group transfusions.Each Blood Transfusion Service should establish a policy for testing and issue of group O platelets to non-O group recipient to avoid chances of development of adverse transfusion reaction.

Anti-TPO-mediated specific features of the placenta immunohistochemical profile and possible mechanisms for fetal loss.

Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-β, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P < .01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-β was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.

Passive antibody transfer from pregnant women to their fetus are maximized after SARS-CoV-2 vaccination irrespective of prior infection

Abstract Pregnancy is associated with a higher risk of adverse symptoms and outcomes for most infectious diseases, including SARS-CoV-2. These adverse risks are also observed in neonates. Antibodies provide protection against SARS-CoV-2 infection, and have been reported after maternal vaccination, maternal infection, and through passive transfer from mother to fetus in utero. However, it is unclear whether the magnitude or quality of maternally-derived fetal antibodies differs in the context of infection or vaccination. Here, we evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from the greater New Orleans area. Histories of SARS-CoV-2 infection or vaccination were obtained. Humoral immunity was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies from naïve subjects. Importantly, vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women. Supported by grants from NIH (NCI U54CA260581-02, NHLBI Grant HL-061007) and USDA (APHIS NBAF NSTP)

Confirmation of the passive transfer of maternal antibodies to calves following vaccination of pregnant cows with an inactivated Mannheimia haemolytica and Bovine herpes virus type 1 vaccine.

The objective of this study was to evaluate the passive transfer of maternal antibodies to calves following vaccination of pregnant cows with an inactivated Mannheimia haemolytica (MH) and Bovine herpes virus type 1 (IBR) vaccine (Bovilis® MH + IBR). Sixty-two pregnant cows were allocated at random to two groups; one group was retained as a negative control group (T01), while the other group (T02) was vaccinated with Bovilis® MH + IBR on two occasions during their third trimester of pregnancy. Following calving, blood samples were collected from calves for the measurement of serum antibody titres to IBR and MH, with samples collected prior to suckling (Day 0) and on days 5 (±2), 14 (±3), 28, 56, 84, 112, 140, 168, 196, 224, 252 and 280. The group mean IBR blocking percentage remained low for T01 calves (calves born to T01 cows) between days 0 and 224 (range 4.5%-15.4%), while the group mean IBR blocking percentage increased for T02 calves (calves born to T02 cows) from 14.3% on Day 0 to 94.9% on Day 5 and remained significantly higher than T01 calves up until Day 252. The group mean MH titre (Log2) for T01 calves increased after suckling to 8.9 on Day 5, before declining and remaining stable (range 5.0-6.5). The group mean MH titre for T02 calves increased after suckling to 13.6 on Day 5 and then gradually declined; however, it remained significantly higher than T01 calves between days 5 and 140. Outcomes from this study have confirmed that colostral transfer of IBR and MH antibodies to newborn calves was successful and a high level of passive immunity was acquired by calves.

COVID-19 Disease in Under-5 Children: Current Status and Strategies for Prevention including Vaccination.

Since the coronavirus disease (COVID-19) pandemic hit the globe in early 2020, we have steadily gained insight into its pathogenesis; thereby improving surveillance and preventive measures. In contrast to other respiratory viruses, neonates and young children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have a milder clinical presentation, with only a small proportion needing hospitalization and intensive care support. With the emergence of novel variants and improved testing services, there has been a higher incidence of COVID-19 disease reported among children and neonates. Despite this, the proportion of young children with severe disease has not increased. Key mechanisms that protect young children from severe COVID-19 disease include the placental barrier, differential expression of angiotensin-converting enzyme 2 (ACE-2) receptors, immature immune response, and passive transfer of antibodies via placenta and human milk. Implementing mass vaccination programs has been a major milestone in reducing the global disease burden. However, considering the lower risk of severe COVID-19 illness in young children and the limited evidence about long-term vaccine safety, the risk-benefit balance in children under five years of age is more complex. In this review, we do not support or undermine vaccination of young children but outline current evidence and guidelines, and highlight controversies, knowledge gaps, and ethical issues related to COVID-19 vaccination in young children. Regulatory bodies should consider the individual and community benefits of vaccinating younger children in their local epidemiological setting while planning regional immunization policies.

RSV A2-Based Prefusion F Vaccine Candidates Induce RSV A and RSV B Cross Binding and Neutralizing Antibodies and Provide Protection against RSV A and RSV B Challenge in Preclinical Models

RSV is divided into two antigenic subtypes, RSV A and RSV B, which is largely based on the variation in the G protein, while the fusion protein F is more conserved and a target for antibody-mediated neutralization. Here we evaluate the breadth of the protective immune responses across RSV A and RSV B subtypes, induced by vaccines based on the RSV A-based fusion protein, stabilized in the prefusion conformation (preF) in preclinical models. Immunization of naïve cotton rats with preF subunit or preF encoded by a replication incompetent Adenoviral 26, induced antibodies capable of neutralizing recent RSV A and RSV B clinical isolates, as well as protective efficacy against a challenge with RSV A and RSV B strains. Similarly, induction of cross-neutralizing antibodies was observed after immunization with Ad26-encoded preF, preF protein or a mix of both (Ad26/preF protein) in RSV pre-exposed mice and African Green Monkeys. Transfer of serum of human subjects immunized with Ad26/preF protein into cotton rats provide protection against challenges with both RSV A and RSV B, with complete protection against both strains observed in the lower respiratory tract. In contrast, almost no protection against RSV A and B infection was observed after the transfer of a human serum pool isolated pre-vaccination. These results collectively show that the RSV A-based monovalent Ad26/preF protein vaccine induced neutralizing antibodies, as well as protection against both RSV A and RSV B subtypes in animals, including by passive transfer of human antibodies alone, suggesting that clinical efficacy against both subtypes can be achieved.