Passive Immunization Research Articles

Effect and Potential Mechanism of Immunotherapy on Cognitive Deficits in Animal Models of Alzheimer's Disease: A Systematic Review and Meta-Analysis

Immunotherapy has been reported to ameliorate Alzheimer's disease (AD) in the animal model; however, the immunologic approaches and mechanisms have not been specifically described. Thus, the systematic review and meta-analysis were conducted to explore the effect and potential mechanism of immunotherapy on AD animal experiments based on behavioral indicators. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Cochrane Collaboration guidelines and the inclusion/exclusion criteria of immunotherapy in animal studies, 15 studies were systematically reviewed after extraction from a collected database of 3,742 publications. Finally, the effect and mechanism of immunotherapy on AD models were described by performing multiple subgroup analyses. After immunotherapy, the escape latency was reduced by 18.15 seconds and the number of crossings over the platform location was increased by 1.60 times in the Morris Water Maze. Furthermore, compared to the control group, active and passive immunization could markedly ameliorate learning and memory impairment in 3 × Tg AD animal models, and active immunization could ameliorate the learning and memory ability of the APPswe/PS1ΔE9 AD animal model. Meanwhile, it could be speculated that cognitive dysfunction was improved by immunotherapy, perhaps mainly via reducing Aβ40, Aβ42, and Tau levels, as well as increasing IL-4 levels. Immunotherapy significantly ameliorated the cognitive dysfunction of AD animal models by assessing behavioral indicators.

Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines

IntroductionRecombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. MethodsThis is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. ResultsAnti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9–150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7–4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. ConclusionsBioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.

Multivariate analysis of FcR-mediated NK cell functions identifies unique clustering among humans and rhesus macaques.

Rhesus macaques (RMs) are a common pre-clinical model used to test HIV vaccine efficacy and passive immunization strategies. Yet, it remains unclear to what extent the Fc-Fc receptor (FcR) interactions impacting antiviral activities of antibodies in RMs recapitulate those in humans. Here, we evaluated the FcR-related functionality of natural killer cells (NKs) from peripheral blood of uninfected humans and RMs to identify intra- and inter-species variation. NKs were screened for FcγRIIIa (human) and FcγRIII (RM) genotypes (FcγRIII(a)), receptor signaling, and antibody-dependent cellular cytotoxicity (ADCC), the latter mediated by a cocktail of monoclonal IgG1 antibodies with human or RM Fc. FcγRIII(a) genetic polymorphisms alone did not explain differences in NK effector functionality in either species cohort. Using the same parameters, hierarchical clustering separated each species into two clusters. Importantly, in principal components analyses, ADCC magnitude, NK contribution to ADCC, FcγRIII(a) cell-surface expression, and frequency of phosphorylated CD3ζ NK cells all contributed similarly to the first principal component within each species, demonstrating the importance of measuring multiple facets of NK cell function. Although ADCC potency was similar between species, we detected significant differences in frequencies of NK cells and pCD3ζ+ cells, level of cell-surface FcγRIII(a) expression, and NK-mediated ADCC (P<0.001), indicating that a combination of Fc-FcR parameters contribute to overall inter-species functional differences. These data strongly support the importance of multi-parameter analyses of Fc-FcR NK-mediated functions when evaluating efficacy of passive and active immunizations in pre- and clinical trials and identifying correlates of protection. The results also suggest that pre-screening animals for multiple FcR-mediated NK function would ensure even distribution of animals among treatment groups in future preclinical trials.

Immunogenicity and protective efficacy of recombinant adenovirus expressing a novel genotype G2b PEDV spike protein in protecting newborn piglets against PEDV.

Porcine epidemic diarrhea (PED) is a highly infectious and economically significant gastrointestinal disorder that affects pigs of all ages. Preventing and controlling PED is achieved by immunizing sows with vaccines, enabling passive piglet immunization via colostrum. The prevalence of G2b porcine epidemic diarrhea virus (PEDV) continues in China despite the use of commercial vaccines, raising questions regarding current vaccine efficacy and the need for novel vaccine development. Adenovirus serotype 5 (Ad5) has several advantages, including high transduction efficiency, a wide range of host cells, and the ability to infect cells at various stages. In this study, we expressed the immunogenic proteins of spike (S) using an Ad5 vector and generated a PED vaccine candidate by inducing significant humoral immunity. The rAd5-PEDV-S prevented PED-induced weight loss, diarrhea, and intestinal damage in piglets. This novel vaccine candidate strain possesses the potential for use in the pig breeding industry.

Passive antibody therapy in emerging infectious diseases.

The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome Coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mAbs were summarized. In addition, the prospects of applying antibody therapy against VOCs was assessed, offering insights into the coping strategies for facing new infectious disease outbreaks.

Prophylactic effect of passive immunotherapy with tau antibody 43D in 3xTg‐AD mice

AbstractBackgroundAccumulation of abnormally hyperphosphorylated tau protein is a histopathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Immunotherapy targeting tau represents a promising disease‐modifying therapeutic strategy for treating AD. We have found that immunization with monoclonal 43D antibody against tau 6‐18 weekly for 6 weeks can inhibit the seeding and spread of tau pathology templated by AD hyperphosphorylated tau, reduce both tau and Aβ pathologies and rescue cognitive impairment in 3xTg‐AD mice at mild to moderate stage of the disease. In this study, we investigated whether tau immunization with 43D prior to the onset of AD‐like pathologies can reduce AD‐like pathologies and improve cognitive function in 3xTg‐AD mice.MethodsWe immunized 3‐ to 4‐month‐old female 3×Tg‐AD mice with nine monthly doses of 15 µg of mouse monoclonal antibody 43D or, as a control, of mouse immunoglobulin G (IgG) intravenously. Age‐matched wild‐type mice treated with mouse IgG were also used as controls. The effect of immunization on cognition was analyzed by using one‐trial novel object recognition test and Morris water maze test, and the effect on tau pathology was assessed by Western blot.ResultsWe found that 3xTg‐AD mice exhibited cognitive impairment as compared to the WT mice, as determined by novel object recognition test and Morris water maze test, and that immunization with 43D antibody improved the cognitive function seen in both tests. Immunization with 43D also decreased tau pathologies in the 3xTg‐AD mice. Additionally, long‐term treatment with 43D antibody did not display side events in 3xTg‐AD mice.ConclusionsThese findings suggest that passive immunization with 43D antibody targeting proximal N‐terminal domain tau 6‐18 may be as both prophylactic and therapeutic approaches for treating AD and related tauopathies.

Long‐term neuropathological effects of amyloid‐β immunization revealed by spatial transcriptomics

AbstractBackgroundModern Alzheimer’s disease (AD) therapeutics include immunization against amyloid‐β (Aβ). Intriguingly, neuropathological examination of the first active Aβ vaccination trial (Elan Pharmaceuticals’ AN1792) showed some patients with evidence of Aβ clearance 15 years post‐vaccination. Yet, these patients progressed to severe dementia before death, possibly due to ongoing tau propagation. The AN1792 trial was halted when some participants developed aseptic meningoencephalitis driven by auto‐aggressive T cells. Imaging features of meningoencephalitis experienced by AN1792 subjects are pathologically reminiscent of amyloid‐related imaging abnormalities (ARIA) that currently hamper clinical trials and the therapeutic use of passive Aβ immunotherapy for AD.MethodHere, we utilized spatial transcriptomics to sequence RNA from formalin‐fixed paraffin‐embedded (FFPE) cortical brain sections from a unique neuropathological cohort of 14 immunized AD cases and a placebo‐control from AN1792. Additional controls included 6 naïve (unimmunized) AD cases and 3 non‐neurological disease controls.ResultWe reveal a cytotoxic and migratory phenotype of infiltrating T cells in the meninges of AD patients immunized against Aβ. Specifically, brain infiltrating T cells express cytotoxic genes (e.g. GZMA), activation genes (e.g. CD74 and B2M), and migratory genes (e.g. ITGAL and VCAM1). Additionally, we discovered genetic signatures that distinguish cortical areas cleared of Aβ in immunized AN1792 subjects.ConclusionWe show that active Aβ immunotherapy induces long‐term adaptive immune effects in the AD cortex.

Characterization of lyophilized equine colostrum

Foals require maternal colostrum in the first hours of life to prevent failure of transfer of passive immunity (FTIP). Innovative storage methods such as lyophilization may enable conservation of colostrum immunoglobulins by a differentiated process of dehydration. The current study aimed to compare the quality of equine colostrum after freezing and after the lyophilization process. Thirty-one pregnant Quarter Horse mares were used. The IgG concentration of frozen and lyophilized colostrum was determined by simple radial immunodiffusion (SRID) and Brix refractometry. The physical-chemical composition (pH, total protein (TP), fat, lactose, salts, total solids (TS), and density) of the samples was evaluated and the lyophilized colostrum reconstitution test was performed. There were no significant differences (P > 0.05) in the variables IgG, fat, lactose, salts, TS, density, and pH between samples measured before and after lyophilization. There was a significant difference (P < 0.05) between the Brix average and the TP of the frozen and lyophilized colostrum samples. Lyophilization resulted in a small reduction (6.55%) in the IgG concentration measured by SRID. A strong positive correlation was observed between colostrum density and IgG concentration by SRID (r = 0.76) and between Brix and IgG concentration by SRID (r = 0.77). In the reconstitution test, the lyophilized colostrum was easily rehydrated in water, with full dilution, and remained stable. Lyophilization could be an alternative for the conservation of mare colostrum, since it is a very efficient process for retaining the physicochemical characteristics of the product, with minimal loss, particularly of IgG.

New Insights on Respiratory Syncytial Virus Prevention.

Respiratory syncytial virus (RSV) is a well-known infant pathogen transmitted mainly by droplets. It is a leading cause of upper respiratory tract infections in children, usually with a mild course of illness. RSV has also been a threat to older people, especially those with underlying medical conditions. For a long time, prevention was limited to passive immunoprophylaxis with palivizumab for high-risk infants. There was a strong need to find other treatment or prevention methods against RSV infections. In addition, after the coronavirus disease 2019 (COVID-19) pandemic, some significant changes in RSV epidemiology have been observed. Researchers noticed the shift in RSV seasonality and age distribution and the increased number of cases in older infants and adults. All of these made the need to find other medical options even stronger. Fortunately, two protein-based vaccines against RSV have successfully passed all phases of clinical trials and have been approved for use by adults and older people. One of them is also approved for infants from birth to 6 months of age (after maternal immunisation during pregnancy) and for pregnant women between 24 and 36 weeks of pregnancy. Also, a new passive immunisation option named nirsevimab (a highly potent monoclonal antibody with a long half-life) is now available for the paediatric group. In this review, we will discuss the previous and current RSV prevention methods in the light of structural discoveries of RSV antigens.

Elizabethkingia anophelis outer membrane vesicles as a novel vaccine candidate against infection: insights into immune response and potential for passive immunity.

Elizabethkingia anophelis, a Gram-negative pathogen, causes infections such as bacteraemia, pneumonia, and neonatal meningitis. The pathogen resists most antimicrobial classes, making novel approaches urgently needed. In natural settings, Gram-negative bacteria secrete outer membrane vesicles (OMVs) that carry important molecules in the bacterial life cycle. These OMVs are enriched with proteins involved in virulence, survival, and carbohydrate metabolism, making them a promising source for vaccine development against the pathogen. This study investigated the efficacy of imipenem-induced OMVs (iOMVs) as a vaccine candidate against E. anophelis infection in a mouse pneumonia model. Mice immunized with iOMVs were completely protected during lethal-dose challenges. Passive immunization with hyperimmune sera and splenocytes conferred protection against lethal pneumonia. Further investigation is needed to understand the mechanisms underlying the protective effects of iOMV-induced passive immunity, such as the action on specific antibody subclasses or T cell subsets.

Timing of Vaccination Impacts Serological Response to COVID-19 Myeloma Patients after BCMA-Targeted CAR T

Whereas COVID-19 mRNA vaccines have shown remarkable efficacy in the prevention of severe disease and mortality in healthy individuals, the effectiveness in cancer patients has been more variable. Patients with multiple myeloma (MM) are at a high risk for severe infection due to disease- or treatment-related immune suppression. Our prior work demonstrated that the immune response to SARS-CoV-2 immunization in MM patients with 2 doses of mRNA vaccine was suboptimal and that a 3rd dose significantly improved neutralization of viral variants. MM patients undergoing treatment targeting BCMA were among those at a higher risk of ineffective immune responses. As BCMA-targeted (CAR T) treatment becomes more widely available, guidance on initiation of vaccination after treatment is needed. To assess the impact of BCMA-targeted CAR T (BCMA CAR T) on the serological immune response to COVID-19, we studied 45 MM patients who received ≥1 dose of a COVID-19 mRNA vaccine after prior BCMA CAR T. We collected demographics, disease/treatment characteristics, and COVID-19 infection/vaccination data via retrospective chart review. We analyzed SARS-CoV-2 spike-binding (anti-spike) IgG level using a validated assay (FDA/EUA approved Kantaro). Cumulative incidence of COVID-19 was analyzed using Kaplan-Meier statistics. All subjects were enrolled to studies approved by the Institutional Review Board at a single US academic hospital. Our cohort consisted of 16 women and 29 men with a median age of 61 years. The patients had received a median 6 lines of treatment and 33/45 (73%) had an ongoing response to BCMA CAR T. Patients received dose 1 at median 567 days after CAR T infusion (range 73-1,374 days). 36 patients (80%) received ≥3 doses and 17 (38%) received ≥4 doses. Across the cohort, anti-spike IgG levels increased from median 8 AU/mL after a single dose to 91, 474 and 612 AU/mL after 2, 3 or 4 mRNA vaccine doses respectively. After 2 doses, 6 patients (of 28 for which the timepoint was available, 21%) had no detectable anti-spike IgG levels, whereas all patients in the cohort had a detectable serological response after ≥3 vaccine doses. We compared the 13 patients (29%) that initiated mRNA vaccination at &amp;lt;12 months (mo) after CAR T infusion (i.e. “early vaccination”) with those who received the first dose after &amp;gt;12 mo. In the early vaccination group, anti-spike IgG levels were significantly lower when measured 0-3 months after 2 vaccine doses (p&amp;lt;0.01). Serological responses were not different when measured after 3 or 4 doses respectively (Fig A). Nevertheless, after 3 vaccine doses, 30% of patients (3/10) in the early vaccination group had anti-spike IgG &amp;lt;100 AU/mL, a level previously shown to be associated with less effective viral neutralization, versus only 5% (1/20) of patients in the group that started vaccination &amp;gt; 12 mo after CAR T. Twenty-four patients (52%) developed a documented COVID-19 infection after vaccination. Of these, 21 (88%) were characterized as mild (i.e. not requiring hospital admission); two patients required hospitalization and recovered, and 1 patient in the early vaccination group passed away from COVID-19. Of note, in the early vaccination group, there was a non-significant trend towards earlier breakthrough infections (Fig B, p=0.16), consistent with the finding of a delayed serological response with suboptimal antibody levels after 2 doses. In this study, all MM patients who initiated mRNA vaccination after prior BCMA CAR T therapy had detectable anti-spike IgG after ≥3 vaccine doses. However, starting vaccination against COVID-19 early (i.e. within 1 year) after CAR T therapy does not result in protective levels of antibody as quickly and to the same extent as when vaccinated &amp;gt;1 year post CAR T infusion. Patients starting vaccination within 12 months need ≥3 doses to achieve comparable serological efficacy to later initiation. A trend towards earlier breakthrough infections suggests that study of neutralizing titers against variants and comprehensive immune phenotyping may be needed to confirm effective immunity in these vulnerable patients. For the first year after CAR T cell therapy, adherence to preventive measures and passive immunization with IVIG with higher titers of anti-spike IgG may be warranted. Analyses comparing this cohort with MM patients receiving other modalities of BCMA-targeted therapy incl. bispecific antibodies are ongoing and will be presented at the meeting.

Designing a novel and combinatorial multi-antigenic epitope-based vaccine “MarVax” against Marburg virus—a reverse vaccinology and immunoinformatics approach

ContextMarburg virus (MARV) is a member of the Filoviridae family and causes Marburg virus disease (MVD) among humans and primates. With fatality rates going up to 88%, there is currently no commercialized cure or vaccine to combat the infection. The National Institute of Allergy and Infectious Diseases (NIAID) classified MARV as priority pathogen A, which presages the need for a vaccine candidate which can provide stable, long-term adaptive immunity. The surface glycoprotein (GP) and fusion protein (FP) mediate the adherence, fusion, and entry of the virus into the host cell via the TIM-I receptor. Being important antigenic determinants, studies reveal that GP and FP are prone to evolutionary mutations, underscoring the requirement of a vaccine construct capable of eliciting a robust and sustained immune response. In this computational study, a reverse vaccinology approach was employed to design a combinatorial vaccine from conserved and antigenic epitopes of essential viral proteins of MARV, namely GP, VP24, VP30, VP35, and VP40 along with an endogenous protein large polymerase (L). MethodsEpitopes for T-cell and B-cell were predicted using TepiTool and ElliPro, respectively. The surface-exposed TLRs like TLR2, TLR4, and TLR5 were used to screen high-binding affinity epitopes using the protein-peptide docking platform MdockPeP. The best binding epitopes were selected and assembled with linkers to design a recombinant multi-epitope vaccine construct which was then modeled in Robetta. The in silico biophysical and biochemical analyses of the recombinant vaccine were performed. The docking and MD simulation of the vaccine using WebGro and CABS-Flex against TLRs support the stable binding of vaccine candidates. A virtual immune simulation to check the immediate and long-term immunogenicity was carried out using the C-ImmSim server. ResultsThe biochemical characteristics and docking studies with MD simulation establish the recombinant protein vaccine construct MarVax as a stable, antigenic, and potent vaccine molecule. Immune simulation studies reveal 1-year passive immunity which needs to be validated by in vivo studies.

Successful transfer of passive immunity: the natural alternative to antibiotics for boosting the survival of intensively reared dairy goat kids

In dairy operations, antibiotics have traditionally been used to treat, prevent, and control diseases. However, given the mounting global crisis of antimicrobial resistance (AMR), farmers are urged to re-assess and reduce their reliance on antibiotics. Thus, this randomized, double-blinded cohort study aimed to estimate the prevalence of failed and successful transfer of passive immunity (FTPI and STPI) in dairy goat kids reared under commercial conditions, and the effects of antibiotic metaphylaxis on the pre-weaning (≤42 d old) mortality in FTPI and STPI kids. Plasma concentration of immunoglobulin G at 1d old (pIgG-24 h) was measured in 747 male Saanen kids for the determination of FTPI and STPI (pIgG-24 h < 12 and ≥12 g/L, respectively). Kids were then randomly divided into two groups: those receiving a single penicillin injection at 1 d old (PEN), and those receiving no treatment (CTR). The mean (±SD) pIgG-24 h and initial BW (IBW) were 17 ± 9.8 g/L and 4.1 ± 0.64 kg. The prevalence of FTPI was 29% (220/747 kids). Gastrointestinal complications were the primary cause of death (41%), followed by septicemia (22%) and arthritis (17%). A single penicillin injection reduced preweaning mortality by 55% (10 vs 22%, PEN vs CTR). However, results suggest that such a decline was mainly driven by the improved survival rates among FTPI kids, which increased by 19% (from 62% in CTR-FTPI to 82% in PEN-FTPI), as opposed to an 8% increase among STPI kids (from 85% in CTR-STPI to 93% in PEN-STPI). Additionally, the odds of mortality ≤ 42 d old were threefold higher in the CTR-FTPI group when compared to both the CTR-STPI and PEN-FTPI groups, suggesting a potential parity between STPI and PEN for mortality rate reduction. Taken together, the results indicate that although metaphylactic antibiotics can halve preweaning mortality, similar improvements are likely to be achieved via increased STPI rates. Furthermore, by targeting metaphylactic interventions to high-risk groups (i.e., those displaying signs of inadequate colostrum intake and/or low birth BW), farmers could reduce treatment costs and mitigate AMR risks. While these findings carry considerable weight for commercial dairy goat practices, their applicability to other systems (i.e., extensive, semi-intensive, mohair, meat systems) warrants further investigation.

Fc-mediated functions and the treatment of severe respiratory viral infections with passive immunotherapy - a balancing act.

Passive immunotherapies have been used to treat severe respiratory infections for over a century, with convalescent blood products from recovered individuals given to patients with influenza-related pneumonia as long ago as the Spanish flu pandemic. However, passive immunotherapy with convalescent plasma or hyperimmune intravenous immunoglobulin (hIVIG) has not provided unequivocal evidence of a clinical benefit for severe respiratory infections including influenza and COVID-19. Efficacy trials, primarily conducted in late-stage disease, have demonstrated inconsistent efficacy and clinical benefit for hIVIG treatment of severe respiratory infections. To date, most serological analyses of convalescent plasma and hIVIG trial samples have focused on the measurement of neutralizing antibody titres. There is, however, increasing evidence that baseline antibody levels and extra-neutralizing antibody functions influence the outcome of passive immunotherapy in humans. In this perspective, findings from convalescent plasma and hIVIG trials for severe influenza, COVID-19 and respiratory syncytial virus (RSV) will be described. Clinical trial results will be discussed in the context of the potential beneficial and deleterious roles of antibodies with Fc-mediated effector functions, with a focus on natural killer cells and antibody-dependent cellular cytotoxicity. Overall, we postulate that treating respiratory viral infections with hIVIG represents a delicate balance between protection and immunopathology.

Maternal mRNA COVID-19 Vaccination During Pregnancy and Delta or Omicron Infection or Hospital Admission in Infants: Test Negative Design Study

(BMJ. 2023;380:e074035) Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) rates are higher in infants than in older children. Passive immunity has been shown to help prevent other infections, such as pertussis, in infants through the transfer of maternal antibodies following vaccination during pregnancy. SARS-CoV-2 antibodies are found to be present in breastmilk, umbilical cord blood, and infant serum specimens following maternal vaccination during pregnancy and infection, and emerging research suggests maternal COVID-19 vaccination reduces infant infection and hospital admission rates. This study aimed to determine whether maternal vaccination during pregnancy with 2 primary doses or 2 primary doses plus booster of the mRNA COVID-19 vaccine series reduces the infection of omicron and delta SARS-CoV-2 and hospital admission of infants within 6 months following delivery.

Increasing insight in the value of repetitive COVID-19 vaccination in patients with haematological malignancies in the Omicron era.

The study by Kevlicius etal. from Lithuania gives further confirmation of the efficacy of booster mRNA COVID-19 vaccination for patients with haemato-oncological malignancies in the Omicron era. The risk of COVID-19 and mortality was considerably reduced when patients received the booster vaccination. The threshold of the humoral response to vaccination that was protective for haemato-oncological patients was defined. In particular, ruxolitinib and anti-CD20 treatments limited the humoral response to the third booster vaccination. These data may influence the clinical management of haemato-oncological patients in future waves of the COVID-19 pandemic, regarding for example the selection of patients for passive immunization against SARS-CoV-2. Commentary on: Kevličius etal. Immunogenicity and clinical effectiveness of mRNA vaccine booster against SARS-CoV-2 Omicron in patients with haematological malignancies: A national prospective cohort study. Br J Haematol 2024;204:497-506.

Exploring the long-term seroprevalence of SARS-CoV-2 antibodies in infants born to women with clinical or laboratory-confirmed COVID-19

IntroductionInfants are at a higher risk of severe illness with COVID-19 infection compared to older children. While COVID-19 vaccination is not recommended for young infants, they can acquire maternally-derived anti-SARS-CoV-2 antibodies passively through the placenta and breastmilk. We described the persistence of infection-induced maternal antibodies in infant circulation at 9–12 months of age. MethodologyThis was a cross-sectional study nested within the INTERCOVID multinational cohort study. For each COVID positive pregnant woman, two unmatched consecutive COVID negative pregnant women were enrolled between April and September 2020. Women with a positive PCR test, radiographic signs consistent with COVID-19, or at least 2 predefined symptoms of COVID-19 were considered as COVID positive. For this nested cross-sectional study, all COVID positive and either one of the COVID negative participants recruited from the Aga Khan University, Pakistan were approached 9–12 months after delivery, and maternal and infant sera were collected for antibody detection. ResultsAltogether, 83 mothers provided consent, of whom 32 (38.6 %) were COVID positive and 51 (61.4 %) were COVID negative during pregnancy. Anti-SARS-CoV-2 antibodies were present in 13 (41 %) infants born to COVID positive and 19 (39 %) infants born to COVID negative mothers (p = 0.87). The presence of reactive antibodies in infants at follow-up was associated with maternal antibodies at follow-up (OR:9.50, 95 % CI:2.03–44.42; p = 0.004). COVID infection occurred in 3 (6 %) infants born to COVID negative mothers while no infant born to a COVID positive mother had a history of infection (p = 0.27). ConclusionThe presence of reactive anti-SARS-CoV-2 antibodies in infants at 9–12 months of age is associated with maternal seropositivity 9–12 months after delivery rather than maternal infection during pregnancy. Further studies are required to validate these findings and assess whether passive immunity in infants is protective against COVID-19 infection.

Cost-effectiveness analysis of nirsevimab and maternal RSVpreF vaccine strategies for prevention of Respiratory Syncytial Virus disease among infants in Canada: a simulation study

The cost-effectiveness of immunisation strategies with a long-acting monoclonal antibody (nirsevimab) and/or a protein-based maternal vaccine (RSVpreF) for protecting infants from Respiratory Syncytial Virus (RSV)-associated illness has not been previously determined for Canada. We estimated the health benefits and cost-effectiveness of nirsevimab for immunising the entire birth cohort, regardless of gestational age or other risk factors. Additionally, we evaluated the health benefits and cost-effectiveness of a combined strategy of year-round vaccination of pregnant women with RSVpreF and immunisation of infants at high risk, including those born preterm or with chronic conditions, with nirsevimab during the RSV season. We developed a discrete-event simulation model, parameterized with the data on medically-attended RSV infections among infants under one year of age from 2010 to 2019, including outpatient care, hospitalisations, and deaths. Intervention scenarios targeting twelve monthly birth cohorts and pregnant women, reflecting the 2021 census data for Ontario, Canada were evaluated over a follow-up time horizon of one year from birth. Taking into account the costs (in 2023 Canadian dollars) associated with RSV-related outcomes, we calculated the net monetary benefit using the quality-adjusted life-year (QALY) gained. Further, we determined the range of price-per-dose (PPD) for nirsevimab and RSVpreF within which the program was cost-effective. Cost-effectiveness analyses were conducted from both healthcare and societal perspectives. Using a willingness-to-pay of CAD$50,000 per QALY gained, we found that immunising the entire birth cohort with nirsevimab would be cost-effective from a societal perspective for a PPD of up to $290, with an annual budget impact of $83,978 for 1113 infants per 100,000 population. An alternative, combined strategy of vaccinating pregnant women and immunising only infants at high risk of severe disease would lead to a lower budget impact of $49,473 per 100,000 population with a PPD of $290 and $195 for nirsevimab and RSVpreF vaccine, respectively. This combined strategy would reduce infant mortality by 76%-85%, comparable to a 78% reduction achieved through a nirsevimab-only program of the entire birth cohort. The PPD for cost-effective programs with nirsevimab was sensitive to the target population among infants. Passive immunisation of infants under 6 months of age with nirsevimab and vaccination of pregnant women with RSVpreF could be a cost-effective strategy for protecting infants during their first RSV season. This study was supported by the Canadian Immunisation Research Network (CIRN) and the Canadian Institutes of Health Research (CIHR). Seyed M. Moghadas acknowledges support from the Natural Sciences and Engineering Research Council of Canada (MfPH and Discovery grants). Alison P. Galvani acknowledges support from the The Notsew Orm Sands Foundation.

Importance, indication and safety of maternal immunization

Vaccination is a very important spectrum for building immunity to fight certain infections. Doing vaccination on the mother as well as the baby, which safeguards both of them, is known as maternal immunization. After childbirth, babies are prone to get infected by many diseases as their immunity is inferior during that time. Over the years, numerous studies have shown that vaccinating mothers can effectively reduce the risk of illnesses such as smallpox, polio, etc. This vaccination process helps strengthen the body's system and enables it to combat these diseases effectively when necessary. This approach works by boosting the transfer of antibodies from the person to the fetus through the placenta, providing passive immunity to the infant during their initial months of life until they become eligible for their own vaccines. In addition to protecting infants, maternal immunization can also help prevent complications for individuals caused by infections that could impact their health and pregnancy outcomes. This review focuses on discussing the significance, indications, and safety of immunization for diseases that pose a high risk to both pregnant individuals and their infants.

Polyvalent passive vaccine candidates from egg yolk antibodies (IgY) of important outer membrane proteins (PF1380 and ExbB) of Pseudomonas fluorescens in fish

Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1β) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.