Impaired anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with diabetes mellitus: A preliminary report

Background and aimsPatients with diabetes mellitus (DM) often demonstrate impaired antibody response to influenza/hepatitis B vaccines. Hence, we compared anti-SARS-CoV-2 antibody response in non-severe COVID-19 patients with and without type 2 diabetes mellitus (T2DM).MethodsRecords of non-severe COVID-19 patients admitted at our institution between April 10, 2020 and May 20, 2020 were retrieved. Qualitative detection of total (IgG + IgM) anti-SARS-CoV-2 antibody was performed using electrochemiluminescence immunoassay in plasma samples collected at least 14 days post-polymerase chain reaction (PCR) confirmation of diagnosis.ResultsThirty-one non-severe COVID-19 patients were included. Nine patients (29%) had T2DM with mean HbA_1c at admission of 8.3 ± 1.0%. Anti-SARS-CoV-2 antibody was estimated at a median of 16 (14–17) days post-PCR confirmation of COVID-19 diagnosis. Only three patients (10%) were seronegative, and all had T2DM. Patients with T2DM were more likely to have non-detectable anti-SARS-CoV-2 antibodies than those without DM (p = 0.019).ConclusionsCOVID-19 patients with T2DM may not undergo seroconversion even after two weeks of diagnosis. Impaired seroconversion could theoretically increase the risk of reinfections in patients with DM. However, the finding requires validation in large-scale studies involving serial estimations of anti-SARS-CoV-2 antibodies in patients with and without DM.     

Vaccines against gonorrhea: Current status and future challenges

Gonorrhea occurs at high incidence throughout the world and significantly impacts reproductive health and the spread of human immunodeficiency virus. Current control measures are inadequate and seriously threatened by the rapid emergence of antibiotic resistance. Progress on gonorrhea vaccines has been slow; however, recent advances justify significant effort in this area. Conserved vaccine antigens have been identified that elicit bactericidal antibodies and, or play key roles in pathogenesis that could be targeted by a vaccine-induced response. A murine genital tract infection model is available for systematic testing of antigens, immunization routes and adjuvants, and transgenic mice exist to relieve some host restrictions. Furthermore, mechanisms by which Neisseria gonorrhoeae avoids inducing a protective adaptive response are being elucidated using human cells and the mouse model. Induction of a Th1 response in mice clears infection and induces a memory response, which suggests Th1-inducing adjuvants may be key in vaccine-induced protection. Continued research in this area should include human testing and clinical studies to confirm or negate findings from experimental systems and to define protective host factors.     

Safety and immunogenicity of a prototype recombinant alpha-like protein subunit vaccine (GBS-NN) against Group B Streptococcus in a randomised placebo-controlled double-blind phase 1 trial in healthy adult women

BackgroundGroup B Streptococcus (GBS) is the leading cause of life-threatening infections in new-borns and may cause invasive disease, stillbirth and preterm delivery during pregnancy. While no licensed vaccine exists, maternal immunization might protect against neonatal disease and adverse pregnancy outcomes. We assessed the safety and immunogenicity of a prototype vaccine consisting of the fused N-terminal domains of the AlphaC and Rib surface proteins of GBS (GBS-NN).MethodsGBS-NN was tested in a randomised, double-blind, placebo-controlled, parallel group, phase I study, in healthy non-pregnant women. A dose-escalation phase, with two doses, four weeks apart, of 10, 50 or 250 µg, administered with or without aluminium hydroxide, was initially assessed (n = 60). This was followed by a dose-confirmation study, where one dose of 100 µg adjuvanted GBS-NN was compared with two doses of either 50 or 100 µg adjuvanted GBS-NN, again administered with four weeks interval between the doses (n = 180). Safety and immunogenicity were monitored for one year.ResultsGBS-NN was well tolerated with some, mostly mild, injection site reactions observed. Adjuvant significantly increased antibody concentrations and the response was boosted by a second dose. The IgG GMCs remained strongly elevated during the whole one-year duration of the study. Maximal responses occurred after two 50 µg doses, resulting in IgG GMC of 16.9 µg/ml at the primary immunological endpoint, twelve weeks after the first dose. For this regimen, 100% and 89% of the subjects achieved antibody levels above the arbitrary thresholds of 1 and 4 µg/ml, respectively. The added beneficial effect of a second dose was most pronounced for subjects with pre-existing IgG levels below the median of the entire cohort.ConclusionThe prototype GBS-NN vaccine was found to be well tolerated and highly immunogenic with an optimal regimen of two doses of 50 µg in the presence of adjuvant. Further development of a maternal vaccine based on the N-terminal domains of the alpha-like protein family of GBS is warranted (NCT02459262).     

Impact of early life exposure to ionizing radiation on influenza vaccine response in an elderly Japanese cohort

The objective of this study was to evaluate effects of whole body radiation exposure early in life on influenza vaccination immune responses much later in life. A total of 292 volunteers recruited from the cohort members of ongoing Adult Health Study (AHS) of Japanese atomic bomb (A-bomb) survivors completed this observational study spanning two influenza seasons (2011–2012 and 2012–2013). Peripheral blood samples were collected prior to and three weeks after vaccination. Serum hemagglutination inhibition (HAI) antibody titers were measured as well as concentrations of 25 cytokines and chemokines in culture supernatant from peripheral blood mononuclear cells, with and without in vitro stimulation with influenza vaccine. We found that influenza vaccination modestly enhanced serum HAI titers in this unique cohort of elderly subjects, with seroprotection ranging from 18 to 48% for specific antigen/season combinations. Twelve percent of subjects were seroprotected against all three vaccine antigens post-vaccination. Males were generally more likely to be seroprotected for one or more antigens post-vaccination, with no differences in vaccine responses based on age at vaccination or radiation exposure in early life. These results show that early life exposure to ionizing radiation does not prevent responses of elderly A-bomb survivors to seasonal influenza vaccine.     

Efficacy of phytol-derived diterpenoid immunoadjuvants over alum in shaping the murine host's immune response to Staphylococcus aureus

The ubiquitous gram-positive bacterium Staphylococcus aureus occupies a unique niche in humans for its ability to survive both as a commensal and a life-threatening pathogen. Its complex relationship with the host and its ability to engender a throng of virulence factors, have hindered the development of a successful vaccine against it. The use of immunoadjuvants to enhance host immunity and prevent the shift from commensalism to pathogenicity is a rational approach for containing infection. The objective of this study was to understand the mechanisms by which alum and two phytol-derived immunoadjuvants, phytanol (PHIS-01) ¹ and phytanyl chloride (PCl) ² shape the interaction between S. aureus and its murine host. We studied the effects of the phytol derivatives, relative to alum, on the induction of inflammatory cytokines and chemokines, recruitment of CD11b⁺ cells, generation of specific anti-S. aureus antibodies and in vitro clearance of S. aureus. Our results showed that both PHIS-01 and PCl were stronger inducers of protective cytokines IL-17 and IL-1β than alum, and far exceeded alum in enhancing anti-S. aureus antibody response. However, both alum and the phytol derivatives (particularly PCl) promoted efficient recruitment of CD11b⁺ cells. Furthermore, PHIS-01, alum and to a lesser extent, PCl were able to up-regulate the expression of key inflammation-related genes that were highly down-regulated by S. aureus alone. In vitro killing assays showed that both PHIS-01 and PCl were far more potent than alum in promoting S. aureus clearance; this indicated their efficiency in shaping an effective anti-S. aureus immune microenvironment. In summary, our study provides evidence for the better effectiveness of phytol-derived immunoadjuvants over alum in enhancing anti-S. aureus immunity.     

Premature ovarian insufficiency and autoimmune diseases

Premature ovarian insufficiency (POI) is a clinical syndrome defined by loss of ovarian activity before the age of 40 years and has a potentially devastating effect upon women's health, both physically and psychologically. An underlying autoimmune disease has been identified in approximately 20% of patients with POI, the most common of which are disorders of the thyroid and adrenal glands. Nevertheless, in the majority of cases, the etiology is unknown. The damage mechanism to the ovary is usually caused by antibodies, and autoimmune POI is usually characterized by cellular infiltration of the theca cells of growing follicles by various inflammatory cells. Yet, other various factors and proteins of unknown clinical significance are present.The major diagnostic tool for otherwise idiopathic POI is the presence of autoantibodies against various ovarian components that strongly support the option of autoimmune etiology of POI.Treatment of the underlying cause of POI is the main strategy, although immunosuppressive therapy should be considered in a selected population of well-defined autoimmune POI and, as in idiopathic POI, in whom the resumption of ovarian activity is possible.     

A prospective,double-blind,randomized, placebo-controlled study on the efficacy and safety of influenza vaccination in myasthenia gravis

Objective

To investigate the efficacy and safety of an influenza vaccination in patients with myasthenia gravis with acetylcholine receptor antibodies (AChR MG).