Host Factors Affecting Generation of Immunity Against Porcine Epidemic Diarrhea Virus in Pregnant and Lactating Swine and Passive Protection of Neonates.

Porcine epidemic diarrhea virus (PEDV) is a highly virulent re-emerging enteric coronavirus that causes acute diarrhea, dehydration, and up to 100% mortality in neonatal suckling piglets. Despite this, a safe and effective PEDV vaccine against highly virulent strains is unavailable, making PEDV prevention and control challenging. Lactogenic immunity induced via the gut-mammary gland-secretory IgA (sIgA) axis, remains the most promising and effective way to protect suckling piglets from PEDV. Therefore, a successful PEDV vaccine must induce protective maternal IgA antibodies that passively transfer into colostrum and milk. Identifying variables that influence lymphocyte migration and IgA secretion during gestation and lactation is imperative for designing maternal immunization strategies that generate the highest amount of lactogenic immune protection against PEDV in suckling piglets. Because pregnancy-associated immune alterations influence viral pathogenesis and adaptive immune responses in many different species, a better understanding of host immune responses to PEDV in pregnant swine may translate into improved maternal immunization strategies against enteric pathogens for multiple species. In this review, we discuss the role of host factors during pregnancy on antiviral immunity and their implications for generating protective lactogenic immunity in suckling neonates.

Maternal vaccination as an additional approach to improve the protection of the nursling: Anti-infective properties of breast milk.

Human milk constitutes a secretion with unique functions of both nourishing the nursling and providing protection against enteric and respiratory infections, mainly due to its content of secretory IgA antibodies but also due to the presence of a plethora of bioactive factors. Specific IgA antibodies are produced locally by plasma cells derived from B lymphocytes that migrate from other mucosae to the mammary gland during lactation, particularly from the gastrointestinal and respiratory tracts. Therefore, here, the authors will provide a comprehensive review of the content and functions of different nutritional and bioactive anti-infectious components from breast milk, such as oligosaccharides, lactoferrin, haptocorrin, α-lactalbumin, k-casein, lysozyme, lactoperoxidase, mucin, fatty acids, defensins, cytokines and chemokines, hormones and growth factors, complement proteins, leukocytes and nucleic acids, including microRNAs, among many others, and the induction of antibody responses in breast milk after maternal vaccination with several licensed vaccines, including the anti-SARS-CoV-2 vaccine preparations used worldwide. Currently, in the midst of the pandemic, maternal vaccination has re-emerged as a crucial source of passive immunity to the neonate through the placenta and breastfeeding, considering that maternal vaccination can induce specific antibodies if performed during pregnancy and after delivery. There have been some reports in the literature about milk IgA antibodies induced by bacterial antigens or inactivated virus vaccines, such as anti-diphtheria-tetanus-pertussis, anti-influenza viruses, anti-pneumococcal and meningococcal polysaccharide preparations. Regarding anti-SARS-CoV-2 vaccines, most studies demonstrate elevated levels of specific IgA and IgG antibodies in milk with virus-neutralizing ability after maternal vaccination, which represents an additional approach to improve the protection of the nursling during the entire breastfeeding period.

Multiplexed flow cytometric approach for detection of anti-SARS-CoV-2 IgG, IgM and IgA using beads covalently coupled to the nucleocapsid protein.

Flow cytometry has emerged as a promising technique for detection of SARS-CoV-2 antibodies. In this study, we developed an innovative strategy for simultaneous detection of immunoglobulin G (IgG), IgM and IgA. The SARS-CoV-2 nucleocapsid protein was covalently bound to functional beads surface applying sulpho-SMCC chemistry. BUV395 anti-IgG, BB515 anti-IgM, biotinylated anti-IgA1/IgA2 and BV421 streptavidin were used as fluorophore conjugated secondary antibodies. Serum and antibodies reaction conditions were optimized for each antibody isotype detection and a multiplexed detection assay was developed. This new cell-free assay efficiently discriminate COVID-19 negative and positive samples. The simultaneous detection of IgG, IgM and IgA showed a sensitivity of 88·5-96·2% and specificity of 100%. This novel strategy opens a new avenue for flow cytometry-based diagnosis.

Comparative analyses of IgG/IgA neutralizing effects induced by three COVID-19 vaccines against variants of concern.

BACKGROUND: Few studies have directly compared virus-specific antibodies and their neutralizing capacity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild type (WT) and circulating variants of concern despite the reported high efficacy of messenger RNA (mRNA)- and vector-based vaccines. OBJECTIVE: We assessed SARS-CoV-2 spike protein region 1 (S1)-specific antibodies of BNT162b2, mRNA-1273, and ChAdOx1 vaccinated as well as convalescent coronavirus disease 2019 (COVID-19) patients. We also determined the neutralization ability against SARS-CoV-2 WT and B.1.1.7 (Alpha), B1.1.7 E484K (Alpha-E484K), B.1.351 (Beta), and B.1.617.2 (Delta) variants. METHODS: Serum samples of 107 fully vaccinated or convalescent individuals were analyzed for anti-SARS-CoV-2-S1 IgG and IgA as well as for total anti-SARS-CoV-2 receptor binding domain Ig. Furthermore, neutralization capacity as 50% and 90% neutralization titer values against SARS-CoV-2 WT virus and circulating variants were determined. RESULTS: We observed a robust IgG response in all participants; however, the highest titers were detected in mRNA-based vaccine recipients. In case of serum IgA responses, the difference between mRNA- and vector-based vaccines or convalescent patients was even more pronounced. Interestingly, all 3 vaccines could neutralize all tested variants of concern in addition to WT virus, but in some individuals, only low or no neutralization, especially against Alpha-E484K and the Delta variant, was detected. CONCLUSION: Our study of the efficacy of various COVID-19 vaccines found that mRNA-1273 had the highest neutralization abilities compared to BNT162b2 and ChAdOx1. COVID-19 convalescent patients demonstrated the most heterogeneous range of antibody titers and neutralization abilities, making it hard to assess protection. Furthermore, a significant positive relation between antibodies and the 50% neutralization titer values for immunized and convalescent individuals was determined.

Differences in Antibody Kinetics and Functionality Between Severe and Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infections.

We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.