Association between hemagglutination inhibition antibody titers and protection against RT-PCR confirmed influenza illness in children 6−35 months of age: statistical evaluation of a correlate of protection

Background Data from a randomized, controlled efficacy trial of an inactivated quadrivalent influenza vaccine in children 6−35 months of age were used to determine whether hemagglutination inhibition (HI) antibody titer against A/H1N1 and A/H3N2 is a statistical correlate of protection (CoP) for the risk of RT-PCR-confirmed influenza associated with the corresponding strain. Methods The Prentice criteria were used to statistically validate strain-specific HI antibody titer as a CoP. The probability of protection was identified using Dunning's model corresponding to a pre-specified probability of protection at an individual level. The group level protective threshold was identified using Siber's approach, leading to unbiased predicted vaccine efficacy (VE). A case-cohort sub-sample was used for this exploratory analysis. Results Prentice criteria confirmed that HI titer is a statistical CoP for RT-PCR-confirmed influenza. Dunning's model predicted a probability of protection of 49.7% against A/H1N1 influenza and 54.7% against A/H3N2 influenza at an HI antibody titer of 1:40 for the corresponding strain. Higher titers of 1:320 were associated with more than 80% probability of protection. Siber's method predicted VE of 61.0% at a threshold of 1:80 for A/H1N1 and 46.6% at 1:113 for A/H3N2. Conclusions The study validated HI antibody titer as a statistical CoP, by demonstrating that HI titer is correlated with clinical protection against RT-PCR-confirmed influenza associated with the corresponding influenza strain and is predictive of VE in children 6−35 months of age.

Human Coronaviruses: Counteracting the Damage by Storm

Over the past 18 years, three highly pathogenic human (h) coronaviruses (CoVs) have caused severe outbreaks, the most recent causative agent, SARS-CoV-2, being the first to cause a pandemic. Although much progress has been made since the COVID-19 pandemic started, much about SARS-CoV-2 and its disease, COVID-19, is still poorly understood. The highly pathogenic hCoVs differ in some respects, but also share some similarities in clinical presentation, the risk factors associated with severe disease, and the characteristic immunopathology associated with the progression to severe disease. This review aims to highlight these overlapping aspects of the highly pathogenic hCoVs—SARS-CoV, MERS-CoV, and SARS-CoV-2—briefly discussing the importance of an appropriately regulated immune response; how the immune response to these highly pathogenic hCoVs might be dysregulated through interferon (IFN) inhibition, antibody-dependent enhancement (ADE), and long non-coding RNA (lncRNA); and how these could link to the ensuing cytokine storm. The treatment approaches to highly pathogenic hCoV infections are discussed and it is suggested that a greater focus be placed on T-cell vaccines that elicit a cell-mediated immune response, using rapamycin as a potential agent to improve vaccine responses in the elderly and obese, and the potential of stapled peptides as antiviral agents.

Phytochemical Constituents Propolis Flavonoid, Immunological Enhancement, Anti-porcine Parvovirus Activities of isolated from the Propolis

Propolis was widely used in health preservation and disease healing, it contains many ingredients. The previous study had been revealed that the propolis has a wide range of efficacy, such as antiviral, immune enhancement, anti-inflammatory and so on, but its antiviral components and underlying mechanism of action remain unknown. In this study, we investigated the chemical composition, and anti-PPV and immunological enhancement of Propolis Flavonoid(PF). Chemical composition of PF was distinguished by UPLC-Q/TOF-MS/MS analysis.The presence and characterized of 26 major components was distinguished in negative ionization modes.To evaluate the effects of PF used as adjuvant on the immune response porcine parvovirus (PPV). Thirty Landrace-Yorkshire hybrid sows were randomly assigned to 3 groups, and the sows in adjuvant groups were intramuscular injected PPV vaccine with 2.0 mL PF adjuvant (PA), oilemulsion adjuvant (OA), respectively. After that, serum hemagglutination inhibition antibody titers, IgM and IgG subclasses, eripheral lymphocyte proliferation activity, and concentrations of cytokines were measured. Results indicated an enhancing effect of PA on IgM, IL-2, IL-4, IFN-γ and the IgG subclass responses. These findings suggested that PA could significantly enhance the immune responses. Furthermore, we screened the chemical components the effective of anti-PPV, Ferulic acid have an excellently anti-PPV effective.

Impact of Immune Priming, Vaccination, and Infection on Influenza A(H3N2) Antibody Landscapes in Children

Background Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination. Methods We enrolled 72 children (aged 7–17 years) in 2015–2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014–2015, with 12 becoming infected with A(H3N2) in 2014–2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015. Results The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014–2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015–2016 vaccination. Conclusions A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection.

Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults

Background Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26.RSV.preF, an adenovirus serotype 26 (Ad26) vector encoding RSV F protein stabilized in its prefusion conformation (pre-F), with a seasonal influenza vaccine in older adults. Methods In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control). Results The coadministration regimen had an acceptable tolerability profile. Reactogenicity was generally higher after Ad26.RSV.preF versus Fluarix, but symptoms were generally transient and mild or moderate. At 28 days after the first vaccination, the upper confidence intervals of the hemagglutination inhibition antibody geometric mean ratio (control/coadministration) for all influenza strains were <2, demonstrating noninferiority. Robust neutralizing and binding antibody responses to RSV A2 were observed in both groups. Conclusions Coadministration of Fluarix with Ad26.RSV.preF vaccine had an acceptable safety profile and showed no evidence of interference in immune response. The results are compatible with simultaneous seasonal vaccination with both vaccines. Clinical Trials Registration NCT03339713.

Coinfection with SARS-CoV-2 and dengue virus: a case report

Background: Since its emergence in China, SARS-CoV-2 has infected more than 15.5 million people worldwide, including in regions where dengue virus (DENV) is hyperendemic such as Latin America and Southeast Asia, including Indonesia. Hence, anticipation for simultaneous infection by DENV and SARS-CoV-2 has been raised.Case presentation: We describe a 68-year-old woman with diabetes mellitus type II who was admitted to the Tangerang District Hospital on 14 April 2020. She lived in a neighborhood where a few people were contracting dengue fever. She presented with five days of fever, malaise, anorexia, nausea, myalgia, and arthralgia. Hematology results revealed anemia, thrombocytopenia, normal leukocyte count, increased neutrophil proportion, and decreased lymphocyte proportion and absolute lymphocyte. Her chest X-ray showed right pericardial infiltrates. Although dengue was clinically suspected, as she met COVID-19 screening criteria, she was also tested for SARS-CoV-2 infection. The patient was treated with ceftriaxone, paracetamol, azithromycin, oseltamivir, and chloroquine. She was clinically improved four days later and was discharged from the hospital on 25 April 2020 after SARS-CoV-2 rRT-PCR was negative on two consecutive samples. Dengue was diagnosed retrospectively based on sero-conversion of dengue IgM and a very high dengue IgG index (Focus Diagnostics®, ELISA), and sero-conversion of dengue IgM and positive IgG (PanBio ®Dengue duo cassette), which was equivalent to high hemagglutination inhibition antibody titer found in secondary dengue infection.Conclusion: The overlapping clinical presentations of COVID-19 and dengue; limited diagnostic capacity of laboratories in resource constrained settings; and complexities of interpreting results make identification of COVID-19 in the dengue endemic setting challenging. Clinicians in endemic areas must maintain a high index of suspicion for the possibility of COVID-19 coinfection with DENV and other tropical pathogens.

Symptoms, Infection Duration, and Hemagglutinin Inhibition Antibody Response in Influenza A Infections

Background Many influenza studies assume that symptomatic and asymptomatic cases have equivalent antibody responses. Methods This study examines the relationship between influenza symptoms and serological response. Influenza-positive index cases and household members in Managua, Nicaragua, during 2012–2017 were categorized by symptom status. Results Antibody response was assessed using hemagglutination inhibition assays (HAI). Among 510 cases, 74.5% had ≥4-fold increase in HAI antibodies, and 75.3% had febrile illness. In a logistic regression model, febrile cases had 2.17 times higher odds of a ≥4-fold titer rise compared to asymptomatic cases (95% confidence interval, 1.02–4.64). Conclusions Studies relying on serological assays may not generalize to asymptomatic infections.

Hemagglutination inhibition antibody titers as a correlate of protection against influenza disease in the 2018/2019 epidemic season in Poland

The aim of this study was to determine the level of antibodies against hemagglutinin of influenza viruses in the sera of people in the seven age groups in the epidemic season 2018/2019 in Poland. The level of anti-hemagglutinin antibodies was determined by hemagglutination inhibition test (HAI). 1050 clinical samples from all over the country were tested. The level of antibodies against influenza viruses was highest in the 10–14 age group for A/Singapore/INFIMH-16-0019/2016 (H3N2) and B/Phuket/3073/2013 Yamagata lineage antigens. These results confirm the circulation of four antigenically different influenza virus strains, two subtypes of influenza A virus – A/Michigan/45/2015 (H1N1)pdm09 and A/Singapore/INFIMH-16-0019/2016 (H3N2) and two lineages of influenza B virus – B/Colorado/06/2017 – Victoria lineage and B/Phuket/3073/2013 Yamagata lineage.