Immunogenicity and safety of inactivated Influenza Split-Virion vaccine administered via a transdermal micro needle system

The purpose of the study was to evaluate the immunogenicity and safety of an inactivated influenza split virion vaccine administered via a transdermal microneedle system. In this Phase 1, single-center, randomized, controlled study, 90 subjects aged 18 to 40 years received influenza vaccine (strains (A/H1N1, A/H3N2, and B) either via a transdermal microneedle system (“patch”; 10 µg) for 5 or 15 minutes or by Intramuscular (IM) injection (15g). Influenza antibody titers were measured by the hemagglutinin inhibition method and compared to EMEA guidelines for influenza vaccines (seroconversion rate, mean increase in hemagglutinin inhibition titer, and percentage of seroprotected subjects). Safety was assessed through local and systemic adverse events, and specific application site events in the transdermal groups. At Day 21, the EMEA criteria were met in all treatment groups for all three influenza strains. The immunogenicity response was similar between all three groups and increased antibody levels persisted to Month 6. The transdermal microneedle system was generally well tolerated, although pinpoint red spots, edema, and erythema were noted after patch removal in most subjects. Influenza vaccination administered via a novel transdermal microneedle system was generally well tolerated and provided similar antibody response using a lower dose than IM injection.

Antibodies to Highly Pathogenic A/H5Nx (Clade 2.3.4.4) Influenza Viruses in the Sera of Vietnamese Residents

To cause a pandemic, an influenza virus has to overcome two main barriers. First, the virus has to be antigenically new to humans. Second, the virus has to be directly transmitted from humans to humans. Thus, if the avian influenza virus is able to pass the second barrier, it could cause a pandemic, since there is no immunity to avian influenza in the human population. To determine whether the adaptation process is ongoing, analyses of human sera could be conducted in populations inhabiting regions where pandemic virus variant emergence is highly possible. This study aimed to analyze the sera of Vietnamese residents using hemagglutinin inhibition reaction (HI) and microneutralization (MN) with A/H5Nx (clade 2.3.4.4) influenza viruses isolated in Vietnam and the Russian Federation in 2017–2018. In this study, we used sera from 295 residents of the Socialist Republic of Vietnam collected from three groups: 52 samples were collected from households in Nam Dinh province, where poultry deaths have been reported (2017); 96 (2017) and 147 (2018) samples were collected from patients with somatic but not infectious diseases in Hanoi. In all, 65 serum samples were positive for HI, at least to one H5 virus used in the study. In MN, 47 serum samples neutralizing one or two viruses at dilutions of 1/40 or higher were identified. We postulate that the rapidly evolving A/H5Nx (clade 2.3.4.4) influenza virus is possibly gradually adapting to the human host, insofar as healthy individuals have antibodies to a wide spectrum of variants of that subtype.

Quaternary Ammonium Salts Based on (-)-Borneol as Effective Inhibitors of Influenza Virus

A new compounds containing 1,7,7-trimethylbicyclo[2.2.1]heptane fragment has been found to exhibit potent inhibitory activity against the influenza A(H1N1) virus. The most potent antiviral compound 10a is a quaternary ammonium salt based on (-)-borneol, with a therapeutic index of more than 500. Mechanism-of-action studies for compound 10a were performed. The compound appeared the most effective when added at the early stages of viral life cycle. In direct hemagglutinin inhibition tests the agent, 10a, was shown to decrease the activity of hemagglutinin of influenza virus A/Puerto Rico/8/34. According to the results of molecular modelling, the lead-compound, 10a, can attach at the binding sites of the stem part of the HA. These results prove that monoterpenoids with 1,7,7-trimethylbicyclo[2.2.1]heptane fragment are prospective natural compounds for the development of antiviral agents.

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.

Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes

Background We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza. Methods This open-label study administered 1 weight-adjusted dose of baloxavir to 107 children aged 1–11 years with laboratory-confirmed, febrile influenza virus infection of ≤48 hours duration. Results Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval, 38.9–62.5 hours), to resolution of fever was 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer). Conclusions A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children. Clinical Trials Registration Japan Pharmaceutical Information Center Clinical Trials Information (Japic CTI-163417).

Continued consideration for high dose influenza vaccine in persons living with HIV

High dose-inactivated influenza vaccine (HD IIV3) is currently recommended only for patients who are 65 or older, whereas other potential risk groups, such as people living with HIV, are excluded from this recommendation. There is a potential that persons living with HIV may be at an increased risk of complications secondary to influenza. HD IIV3 has been associated with increased rates of seroconversion, seroprotection and hemagglutinin inhibition geometric mean titers in comparison to standard dose-inactivated influenza vaccine in this population. Despite the major impact that combination antiretroviral therapy has on this population, further consideration of HD IIV3 may be valuable until virological suppression is widely achieved.

Identification of human vaccinees that possess antibodies targeting the egg-adapted hemagglutinin receptor binding site of an H1N1 influenza vaccine strain

Human influenza viruses passaged in eggs often acquire mutations in the hemagglutinin (HA) receptor binding site (RBS). To determine if egg-adapted H1N1 vaccines commonly elicit antibodies targeting the egg-adapted RBS of HA, we completed hemagglutinin-inhibition assays with A/California/7/2009 HA and egg-adapted A/California/7/2009-X-179A HA using sera collected from 159 humans vaccinated with seasonal influenza vaccines during the 2015-16 season. We found that ~5% of participants had ≥4-fold higher antibody titers to the egg-adapted viral strain compared to wild type viral strain. We used reverse-genetics to demonstrate that a single egg-adapted HA RBS mutation (Q226R) was responsible for this phenotype.

Hubungan Status Frailty dengan Serokonversi dan Seroproteksi Vaksin Influenza pada Populasi Usia Lanjut

Pendahuluan. Infeksi masih merupakan ancaman yang serius bagi dunia kesehatan saat ini, terutama bagi populasi khusus seperti usia lanjut. Usia dinyatakan sebagai salah satu faktor prediktor dalam keberhasilan vaksinasi. Semakin tua usia seseorang, respon imunnya akan semakin buruk. Respon yang berbeda pada usia lanjut ini diperkirakan karena frailty dan kejadian immunosenescense yang mendasarinya. Penelitian ini dilakukan untuk mengetahui hubungan status frailty dengan respon imun pascavaksinasi influenza pada populasi usia lanjut.Metode. Studi kohort retrospektif ini mengambil data dari penelitian induk dengan subjek usia lanjut berusia ≥60 yang tergabung dalam Posyandu Lansia di 4 kelurahan di Kecamatan Pulo Gadung, Jakarta Timur. Status frailty ditentukan berdasarkan kuisoner Frailty Index 40 Items (FI-40). Vaksin Influenza yang dievaluasi adalah vaksin influenza trivalen inaktif. Serokonversi didefinisikan sebagai peningkatan titer inhibisi hemagglutinin sebanyak 4x lipat. Seroproteksi didefinisikan sebagai titer inhibisi hemagglutinin ≥1:40.Hasil. Terdapat 140 subjek penelitian. Tingkat serokonversi vaksin influenza pada kelompok frail, pre-frail dan sehat adalah 37,9%, 39% dan 60%. Tingkat seroproteksi vaksin influenza pada kelompok frail, pre-frail dan sehat adalah 80%, 92,2% dan 94,8% . Risiko relatif (RR) kelompok pre-frail/frail untuk kejadian tidak serokonversi adalah 0,93 (IK 95% 0,72-1,02) dan RR untuk kejadian tidak seroproteksi adalah 1,7 ( IK 95% 0,5-6,2).Simpulan. Tidak ditemukan hubungan antara status frailty dengan serokonversi dan seroproteksi vaksin influenza pada populasi usia lanjut.Kata Kunci: Frailty, pre-frail, frail, serokonversi, seroproteksi, usia lanjut, vaksin influenza Correlation of Frailty Status with Influenza Vaccine Seroconversion and Seroprotection among Elderly PopulationIntroduction. Infection is still considered as a serious health threat in the world, especially among the elderly. Age was identified as one of the predictor factors for successfull vaccination. Immune response would decrease in older people. A different response in the elderly is expected from frailty and underlying immunosenescense events. This study was conducted to determine the relationship with the Frailty status after the vaccination immune response of influenza in the elderly population. Methods. This retrospective cohort study was conducted using secondary data from the parent study of elderly subjects age ≥60 years who live in the community of Posyandu lansia in Pulo Gadung Region, East Jakarta. Frailty status was stated by Frailty Index 40 Items (FI-40). The influenza vaccine evaluated was the Trivalent Inactivated Vaccine. Seroconversion defined as four fold increase hemagglutinin inhibition titre. Seroprotection defined as Hemagglutinin Inhibition titer ≥1:40. Results. There are 140 subject included in this study. Seroconversion influenza vaccine rate in frail, pre-frail, and robust group are 37.9%, 39%, 60%, respectively. Seroprotection rate in frail, pre-frail, and robust group are 80%, 92.2%, 94.8%, respectively. Relative Risk (RR) pre-frail/frail group for not seroconverted is 0.93 (CI 95% 0.72-1.02), and RR for not seroprotected is 1,7 ( CI 95% 0.5-6.2). Conclussions. There is no association between frailty status and seroconversion nor seroprotection of influenza vaccine in elderly population. Keywords: elderly, frail, influenza vaccine, pre-frail, seroconversion, seroprotection