Adjuvant Effect of Orally Applied Preparations Containing Non-Digestible Polysaccharides on Influenza Vaccination in Healthy Seniors: A Double-Blind, Randomised, Controlled Pilot Trial

Senior individuals can suffer from immunosenescence and novel strategies to bolster the immune response could contribute to healthy ageing. In this double-blind, randomised, controlled pilot trial, we investigated the ability of non-digestible polysaccharide (NPS) preparations to enhance the immune response in a human vaccination model. In total, 239 subjects (aged 50–79 years) were randomised to consume one of five different NPS (yeast β-glucan (YBG), shiitake β-glucan (SBG), oat β-glucan (OBG), arabinoxylan (AX), bacterial exopolysaccharide (EPS)) or control (CTRL) product daily for five weeks. After two weeks of intervention, subjects were vaccinated with seasonal influenza vaccine. The post-vaccination increases in haemagglutination inhibition antibody titres and seroprotection rate against the influenza strains were non-significantly enhanced in the NPS intervention groups compared to CTRL. Specifically, a trend towards a higher mean log2 fold increase was observed in the AX group (uncorrected p = 0.074) combined with a trend for an increased seroprotection rate, AX group (48.7%) compared to CTRL (25.6%) (uncorrected p = 0.057), for the influenza A H1N1 strain. Subjects consuming AX also had a reduced incidence of common colds compared to CTRL (1 vs. 8; p = 0.029 in Fisher exact test). No adverse effects of NPS consumption were reported. The findings of this pilot study warrant further research to study AX as an oral adjuvant to support vaccine efficacy.

Fifth-week immunogenicity and safety of anti-SARS-CoV-2 BNT162b2 vaccine in patients with multiple myeloma and myeloproliferative malignancies on active treatment: preliminary data from a single institution

Background Safety and immunogenicity of BNT162b2 mRNA vaccine are unknown in hematological patients; both were evaluated prospectively in 42 patients with multiple myeloma (MM) and 50 with myeloproliferative malignancies (MPM) (20 chronic myeloid leukemias and 30 myeloproliferative neoplasms), all of them on active anti-cancer treatment, in comparison with 36 elderly controls not suffering from cancer. Subjects serologically and/or molecularly (by nasal/throat swab) positives at basal for SARS-CoV-2 were excluded. Primary endpoint was to compare titers of neutralizing anti-SARS-CoV-2 IgG and seroprotection rates among the cohorts at 3 and 5 weeks from first dose. Methods Titration was done using LIAISON® SARS-CoV-2 S1/S2 IgG test, a quantitative chemiluminescent immunoassay approved by FDA on the basis of robust evidences of concordance (94.4%) between the test at cutoff of 15 AU/mL and the Plaque Reduction Neutralization Test 90% at 1:40 ratio. Cutoff of 15 AU/mL was assumed to discriminate responders to vaccination with a protective titer. Cohorts were compared using Fisher’ exact test and the Mann–Whitney test as appropriated. Geometric mean concentrations (GMCs), geometric mean ratios and response rates after 1st and 2nd dose were compared in each cohort by Wilcoxon and McNemar tests, respectively. Results At 5 weeks, GMC of IgG in elderly controls was 353.3 AU/mL versus 106.7 in MM (p = 0.003) and 172.9 in MPM patients (p = 0.049). Seroprotection rate at cutoff of 15 AU/mL was 100% in controls compared to 78.6% in MM (p = 0.003) and 88% in MPM patients (p = 0.038). In terms of logarithm of IgG titer, in a generalized multivariate linear model, no gender effect was observed (p = 0.913), while there was a significant trend toward lower titers by increasing age (p < 0.001) and in disease cohorts with respect to controls (MM: p < 0.001 and MPM: p < 0.001). An ongoing treatment without daratumumab was associated with higher likelihood of response in MM patients (p = 0.003). No swabs resulted positive on each time point. No safety concerns were observed. Conclusions BNT162b2 has demonstrated to be immunogenic at different extent among the cohorts. Response was 88% and robust in MPM patients. MM patients responded significantly less, particularly those on anti-CD38-based treatment. These latter patients should be advised to maintain masks and social distancing regardless of vaccination status, and their cohabiting family members need to be vaccinated in order to reduce the risk of contagion from the family. Additional boosters and titer monitoring could be considered. Trial registration Study was formally approved by the IRCCS Central Ethical Committee of Regione Lazio in January 2021 (Prot. N-1463/21).

Adjuvanted recombinant hemagglutinin H7 vaccine to highly pathogenic influenza A(H7N9) elicits high and sustained antibody responses in healthy adults

An unprecedented number of human infections with avian influenza A(H7N9) in the fifth epidemic wave during the winter of 2016–2017 in China and their antigenic divergence from the viruses that emerged in 2013 prompted development of updated vaccines for pandemic preparedness. We report on the findings of a clinical study in healthy adults designed to evaluate the safety and immunogenicity of three dose levels of recombinant influenza vaccine derived from highly pathogenic A/Guangdong/17SF003/2016 (H7N9) virus adjuvanted with AS03 or MF59 oil-in water emulsions. Most of the six study groups meet the FDA CBER-specified vaccine licensure criterion of 70% seroprotection rate (SPR) for hemagglutination inhibition antibodies to the homologous virus. A substantial proportion of subjects show high cross-reactivity to antigenically distinct heterologous A(H7N9) viruses from the first epidemic wave of 2013. These results provide critical information to develop a pandemic response strategy and support regulatory requirements for vaccination under Emergency Use Authorization.

Immunogenicity and safety of rapid scheme vaccination against tick-borne encephalitis in HIV-1 infected persons

Tick-borne encephalitis (TBE) is a vector-borne infection associated with a variety of potentially serious complications and sequelae. Vaccination against TBE is strongly recommended for people living in endemic areas. There are two TBE vaccination schemes – standard and rapid – which differ in the onset of protection. With vaccination in a rapid schedule, protection starts as early as 4 weeks after the first dose and is therefore especially recommended for non-immune individuals travelling to endemic areas. Both schemes work reliably in immunocompetent individuals, but only little is known about how TBE vaccination works in people with HIV infection. Our aim was to assess the immunogenicity and safety of the rapid scheme of TBE vaccination in HIV-1 infected individuals. Concentrations of TBE-specific IgG > 126 VIEU/ml were considered protective. The seroprotection rate was 35.7% on day 28 and 39.3% on day 60. There were no differences between responders and non-responders in baseline and nadir CD4 + T lymphocytes. No serious adverse events were observed after vaccination. The immunogenicity of the TBE vaccination was unsatisfactory in our study and early protection was only achieved in a small proportion of vaccinees. Therefore, TBE vaccination with the rapid scheme cannot be recommended for HIV-1 infected individuals.

21. Current and Nadir CD4+ Counts Are Associated with Heplisav-B Seroprotection Rates in People with HIV

Background A two-dose hepatitis B (HBV) vaccine with an immunostimulatory adjuvant (HBV-ISS, Heplisav-B), was FDA approved in 2017 for adults 18 years and older. In randomized controlled trials (RCTs), HBV-ISS demonstrated a seroprotection rate (SPR) of 90–95% versus 65–80% for Engerix-B (HBV-Eng). No RCTs, however, included people with HIV (PWH), and the SPR and its predictors in this population are unknown. Methods This retrospective cohort study enrolled PWH ages 18 years and older without current HBV seroprotection at an HIV clinic at a tertiary care center. HBV seroprotection was defined as an anti-HBV surface antibody level &gt;= 10 mIU/mL. Patients without follow-up titers after immunization were excluded. The primary outcome was the SPR, the proportion of patients with HBV seroprotection at any point following the first HBV-ISS vaccination. Results Among the 51 PWH included, 50 received 2 doses of HBV-ISS (1 patient who received 1 dose developed seroprotection) (Table 1). Median time to antibody titer measurement was 11 weeks (IQR 7–19 weeks). Median age was 59 years, 90% were men, and 96% had VL &lt; 200. There were no pregnant or breastfeeding patients. The SPR was 82% (42/51) in the cohort, and 86% (38/44) when patients with significant non-HIV immunosuppression (decompensated cirrhosis, solid organ transplantation, active chemotherapy) were excluded. There were no significant differences in SPR based on age, sex, BMI, diabetes mellitus, chronic kidney disease, history of remote anti-HBV surface or core antibody positivity, or prior HBV vaccination (Table 2). Lower current and nadir CD4+ counts were associated with progressively lower SPRs (P for trend &lt; 0.0001 for both) (Figure 1). Table 1. Baseline Demographics and Characteristics Table 2. Seroprotection Rate (SPR) by Variables of Interest Figure 1. Seroprotection Rate (SPR) by Current and Nadir CD4+ Count Conclusion The SPR from HBV-ISS in PWH appears comparable to the immunocompetent patients included in RCTs, especially when patients with significant non-HIV immunosuppression are excluded. The SPR demonstrated in this single-arm, retrospective study was higher than that of HBV-Eng in immunocompetent patients, and consideration should be given to establishing HBV-ISS as first-line HBV vaccination in PWH. Finally, SPR is significantly reduced in those with lower current and nadir CD4+ counts. Further research on the effectiveness of a repeat vaccination series or higher dosing in these subgroups is needed. Disclosures Jennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)

7. Two-Dose 4CMenB Vaccination in Adolescents Elicits a Bactericidal Activity against 15 Outbreak-Representative Meningococcal Strains

Background Meningococcal outbreaks have often been associated with N. meningitidis serogroup B (MenB) in high-income countries. We examined whether antibodies elicited by the 4-component MenB vaccine (4CMenB) in adolescents could induce complement-mediated bacterial killing of a panel of 14 genetically diverse MenB strains representative of outbreaks that occurred from 2001 to 2016 (11 from the US, 2 from the UK, and 1 from France). One N. meningitidis serogroup W (MenW) hyperendemic strain (UK, 2011) was also included in the analysis. Methods In a previous multicenter study (NCT02212457), adolescents aged 10-18y received 2 4CMenB doses 2 months apart. We tested individual sera collected from a subgroup of 20 US participants at pre-vaccination and 1 month post-second dose in a serum bactericidal assay with human complement (hSBA) against the meningococcal strain panel. Similarly, sera collected from 23 Chilean adolescents aged 11-17y (NCT00661713) were tested in a hSBA against a subset of 4 strains (3 from the US, 1 from the UK). Results At baseline, the percentage of US subjects with seroprotective titers (hSBA ≥ 1:4) ranged from 5% to 35%. One month after 4CMenB series completion, 65% to 100% had seroprotective titers (hSBA ≥ 1:4) against 11 out of the 14 MenB tested strains. The seroprotection rate was 45%, 25%, and 15% against the 3 remaining MenB strains. Against MenW, the percentage of adolescents with hSBA titers ≥ 1:4 was 15% at baseline and 95% one month after series completion. No significant changes in the percentage of subjects were observed when analysing hSBA titers ≥ 1:8. Moreover, the subset analysis indicated similar results for US and Chilean subjects for 3 out of 4 strains: the percentage of US vs Chilean subjects with hSBA titers ≥ 1:4 was 100% vs 100%; 80% vs 74%; 45% vs 52%. For the 4th strain, 65% of US subjects vs 91% of Chilean subjects showed a hSBA ≥ 1:4. Conclusion 4CMenB elicited bactericidal antibodies against a panel of 14 outbreak-representative MenB strains and 1 MenW hyperendemic strain in US adolescents. No major differences were detected in the bactericidal activity of Chilean subjects vaccinated with 4CMenB when tested against a subset of 4 MenB outbreak strains, suggesting that the immune response to 4CMenB is comparable in adolescents from different geographic areas. Disclosures Alessia Biolchi, n/a, GSK (Employee) Sara Tomei, n/a, GSK (Employee) Laura Santini, n/a, GSK (Employee) Rita La Gaetana, n/a, GSK Vaccines (Employee, Shareholder) Elena Mori, n/a, GSK (Employee) Patricia Novy, PhD, GSK (Employee, Shareholder) Rino Rappuoli, PhD, GSK (Employee) Rafik Bekkat-Berkani, M.D, GSK (Employee, Shareholder) Marzia Monica Giuliani, n/a, GSK (Employee, Shareholder) Mariagrazia Pizza, Biological Sciences, PhD, GSK Vaccines (Employee)

A Randomized Phase 4 Study of Immunogenicity and Safety After Monovalent Oral Type 2 Sabin Poliovirus Vaccine Challenge in Children Vaccinated with Inactivated Poliovirus Vaccine in Lithuania

Background Understanding immunogenicity and safety of monovalent type 2 oral poliovirus vaccine (mOPV2) in inactivated poliovirus vaccine (IPV)–immunized children is of major importance in informing global policy to control circulating vaccine-derived poliovirus outbreaks. Methods In this open-label, phase 4 study (NCT02582255) in 100 IPV-vaccinated Lithuanian 1–5-year-olds, we measured humoral and intestinal type 2 polio neutralizing antibodies before and 28 days after 1 or 2 mOPV2 doses given 28 days apart and measured stool viral shedding after each dose. Parents recorded solicited adverse events (AEs) for 7 days after each dose and unsolicited AEs for 6 weeks after vaccination. Results After 1 mOPV2 challenge, the type 2 seroprotection rate increased from 98% to 100%. Approximately 28 days after mOPV2 challenge 34 of 68 children (50%; 95% confidence interval, 38%–62%) were shedding virus; 9 of 37 (24%; 12%–41%) were shedding 28 days after a second challenge. Before challenge, type 2 intestinal immunity was undetectable in IPV-primed children, but 28 of 87 (32%) had intestinal neutralizing titers ≥32 after 1 mOPV2 dose. No vaccine-related serious or severe AEs were reported. Conclusions High viral excretion after mOPV2 among exclusively IPV-vaccinated children was substantially lower after a subsequent dose, indicating induction of intestinal immunity against type 2 poliovirus.

STUDY OF IMMUNE RESPONSE AFTER HEPATITIS B VACCINATION IN DOCTORS

Background: Aim of our study was to evaluate the immune response after hepatitis B vaccination and to determine the duration of protective levels of HBsAb titre in doctors. From our study we concluded that hepatitis-B vaccine gives protection for more than 10 years after primary vaccination and booster dose of Hepatitis-B vaccine is not required in immunocompetent persons after primary vaccination. Method: In this study total 100 doctors of our institution were included who were vaccinated against hepatitis B. Data were obtained regarding age, sex, weight, height, BMI and duration of vaccination period. Doctors with no prior vaccination or incomplete vaccination or those who took booster vaccination were excluded from this study. Results: The mean titre was observed to be higher in 30 to 34 years of age group (584.42±4.03.21) as compared to age group of less than 25 and greater than 40 years. Moreover, males were observed to have higher mean titre as compared to females. (411.64± 417.27 vs 333.66± 431.49) but not statistically significant. Similar with age and sex, duration of vaccination status was also not statistically significant. When we compared the duration of vaccination status with age group , mean titre was more in ≥30 years of age group as compared to <30 years (younger age groups) but statistically significant relation was observed only with the 1 month to <5 years of duration. Conclusion: From our study we concluded that hepatitis-B vaccinegives protection for more than 10 years after primary vaccination and booster dose of Hepatitis-B vaccine is not required inimmuno-competent persons after primary vaccination. Keywords: HbsAg titre , HepatitsB vaccine , seroprotection rate.

A Double-blind, Randomized Phase 2 Controlled Trial of Intradermal Hepatitis B Vaccination With a Topical Toll-like Receptor 7 Agonist Imiquimod, in Patients on Dialysis

Background Patients on dialysis are hyporesponsive to the hepatitis B virus vaccines (HBVv). We examined intradermal (ID) HBVv Sci-B-Vac, with topical Toll-like receptor 7 (TLR7) agonist imiquimod pretreatment in dialysis patients. Methods We enrolled and prospectively followed adult patients on dialysis between January 2016 and September 2018. Eligible patients were randomly allocated (1:1:1) into 1 treatment group, topical imiquimod cream followed by ID HBVv (IMQ + ID); and 2 control groups: topical aqueous cream (placebo) followed by ID HBVv (AQ + ID) or topical aqueous cream followed by intramuscular HBVv (AQ + IM). The primary endpoint was the seroprotection rate (hepatitis B surface antibody ≥10 mIU/mL) at 52 weeks. Results Ninety-four patients were enrolled, among which 57.4% were previous nonresponders. Seroprotection rate was significantly better at week 52 for the IMQ + ID group with 96.9% compared to 74.2% and 48.4% for AQ + ID and AQ + IM groups, respectively (P &lt; .0001). The geometric mean concentration was significantly higher at week 52 for the IMQ + ID group: 1135 (95% confidence interval [CI], 579.4–2218.2) mIU/mL, compared to 86.9 (95% CI, 18.5–409.3) mIU/mL and 7.2 (2.0–26.5) mIU/mL for the AQ + ID and AQ + IM groups, respectively (P &lt; .0001). IMQ + ID vaccination (odds ratio, 3.70 [95% CI, 1.16–11.81]; P = .027) was the only factor independently associated with higher 52-week seroprotection rate. Adverse reaction was infrequent. Conclusions Pretreatment with topical imiquimod before ID HBVv Sci-B-Vac was safe with favorable seroprotection in dialysis patients. Clinical Trials Registration NCT02621112.