SEROPROTECTION RATE OF HAEMOPHILUS INFLUENZAE TYPE B CONJUGATE VACCINE AND ASSOCIATED CLINICAL OUTCOMES AMONG NIGERIAN CHILDREN AGED 6 TO 23 MONTHS.

Introduction: Haemophilus influenzae type b (Hib) causes invasive infections almost exclusively in under- fives with those aged 6-23 months being the most vulnerable. In Nigeria, it is estimated to cause nearly 400,000 annual infections and another 30,000 under-five mortality attributable to pneumonia and meningitis alone. The Hib Conjugate Vaccine (HCV) is in widespread use to combat these devastating infections. Data on its impact in Nigeria is grossly scanty. This study evaluated the seroprotection rates (SPR) of HCV and associated clinical outcomes among children aged 6-23 months in Obi L.G.A. of Nasarawa State, Nigeria. Methods: A cross-sectional study of 267 children aged 6-23 months who had completed three doses of HCV. They were enrolled via a two-staged household-level cluster sampling. Relevant sociodemographic and clinical data were obtained using structured questionnaires and serum samples collected were analysed serologically for antipolyribosylribitol phosphate (anti-PRP) antibodies using ELISA. Results: The overall SPRs against invasive Hib disease and Hib nasopharyngeal colonization were 74.2% and 26.2%, respectively. The overall geometric mean titre (GMT) of anti-PRP was 1.85 µg/mL (95%CI: 1.60-2.14) and across age groups, GMTs were >1 µg/mL-the threshold for long-term protection against invasive Hib disease. Rates/duration of healthcare admissions and average episodes of probable Hib disease syndromes were lower in seroprotected but not statistically different from non-seroprotected children. Conclusion: The demonstrated anti-PRP titres and Seroprotection Rates infer a very good HCV efficacy in Nigerian children. The lack of significant difference in clinical outcomes may be attributable to nonspecificity.

Assessment of immunogenicity and safety across two manufacturing lots of a 3-antigen hepatitis B vaccine, Sci-B-Vac®, compared with Engerix-B® in healthy Asian adults: A phase 3 randomized clinical trial.

BACKGROUND: Sci-B-Vac®, a 3-antigen hepatitis B vaccine (3A-HBV), contains all three recombinant hepatitis B virus (HBV) envelope proteins (S, pre-S1, and pre-S2). In 2005, 3A-HBV manufacturing transferred facilities (A to B), where it continues to be manufactured. METHODS: This phase 3, single-blind, randomized study, conducted at one site in Vietnam, compared efficacy and safety among two 3A-HBV lots, lot A and lot B, and a single-antigen hepatitis B vaccine (1A-HBV), Engerix-B®. Primary objective was to demonstrate equivalence at day 210 of two 3A-HBV lots in seroprotection rate (SPR; defined as percentage of participants achieving hepatitis B surface antigen antibody [anti-HBs] titers ≥ 10 mIU/mL). Secondary objectives were assessing immunogenicity at days 180, 210, and 360, and safety of 3A-HBV. RESULTS: 3A-HBV SPR equivalence was demonstrated at day 210 (lot A: 97.3% [95% CI: 92.4%, 99.4%] vs. lot B: 100.0% [97.0%, 100.0%]). Compared to 1A-HBV, lot B SPR was higher at day 180 (98.3% vs. 81.2%; difference: 17.1% [9.7%, 24.6%]) and non-inferior at day 210 (100% vs. 98.3%; difference: 1.7% [-0.6%, 4.1%]). 3A-HBV lot B showed the same SPR after 2 doses (98.3%) as 1A-HBV after 3 doses (98.3%). Adverse events (AEs) were comparable with both 3A-HBV lots (lot A: 68.7% vs. lot B: 54.2%), but higher than 1A-HBV (35.3%). Vaccination-related AEs included transient injection site pain (38.9%), myalgia (9.3%), and fatigue (7.5%). Eight serious AEs were reported (lot A: 3/134 [2.2%]; lot B: 1/134 [0.8%]; 1A-HBV: 4/133 [2.3%]). One serious AE, syncope, was noted as probably related to study vaccine, lot B. CONCLUSIONS: The two 3A-HBV lots had equivalent immunogenicity, but lot B elicited faster onset of seroprotection and higher anti-HBs titers than both lot A and 1A-HBV in an Asian population. This supports 3A-HBV lot B as an effective choice for HBV vaccination, with a favorable safety profile. ClinicalTrials.gov: NCT04531098.

CpG-Adjuvanted Hepatitis B Vaccine (HEPLISAV-B®) Update.

Introduction: HEPLISAV-B is a hepatitis B vaccine composed of rHBsAg mixed with a synthetic oligonucleotide containing CpG motifs that stimulate innate immunity through TLR9. This vaccine was recently approved by FDA in view of its superior efficacy.Areas covered: Published literature on HEPLISAV-B was critically reviewed. Four randomized controlled trials among 7,056 subjects receiving 2 doses of HEPLISAV-B and 3,214 subjects receiving 3 doses of Engerix-B showed superior seroprotection rate (SPR) (anti-HBs ≥10 mIU/mL) of 90-100%, compared with 71-90% in those receiving Engerix-B. Furthermore, the seroprotection rate was also significantly higher in HEPLISAV-B compared with Engerix-B recipients in persons with traditionally poor vaccine responses such as older adults, diabetics, and those with chronic kidney disease. The safety profiles among 9,871 subjects were similar between HEPLISAV-B and Engerix-B .Expert opinion: HEPLISAV-B, a CpG adjuvant mixed with HBsAg, is more efficacious and produced earlier seroprotection compared to existing vaccines, with a favorable safety profile. The shorter, two-dose regimen, earlier seroprotection, higher adherence, and a higher seroprotection rate, especially in populations with traditionally poor vaccine response, makes this an important therapeutic option in hepatitis B vaccination.

Factors Influencing Persistence of Diphtheria Immunity and Immune Response to a Booster Dose in Healthy Slovak Adults.

We assessed the long-term persistence of humoral immunity against diphtheria in adults with childhood vaccination and the immunogenicity of a booster dose considering demographic, behavioural and vaccinating factors. We conducted a trial in 200 healthy Slovak adults aged 24-65 years, immunised against diphtheria in childhood and against tetanus at regular 10-15 year intervals, and receiving a dose of a tetanus-diphtheria toxoid vaccine. The response was determined by ELISA antibody concentrations of paired sera before and at 4 weeks post-vaccination. A seroprotection rate of 21% (95% confidence interval, CI 15.6-27.3%) was found in adults up to 59 years since the last vaccination with seroprotective levels of antibodies against diphtheria ≥0.1 IU/mL and a geometric mean concentration of 0.05 IU/mL. Conversely, seropositive levels ≥0.01 IU/mL were observed in 98% of adults (95% CI 95-99.5%). Booster-induced seroprotection was achieved in 78% of adults (95% CI 71.6-83.5%) clearly depending on pre-booster antibody levels correlating with age and time since the last vaccination. Moreover, only 54.2% of smokers and 53.3% of patients on statins exhibited seroprotection. Booster vaccination against diphtheria was unable to confer seroprotection in all recipients of only childhood vaccination.

Booster influenza vaccination confers additional immune responses in an elderly, rural community-dwelling population.

This study aimed to examine the effects of a booster vaccination in elderly people using 2 doses of trivalent inactivated influenza vaccine during the 2012-2013 influenza epidemic. Seroprotection rates against the A(H1N1)pdm09 strain in younger elderly people (aged 61-75 years) and the A(H3N2) and B strains in both younger elderly people (aged 61-75 years) as well as very elderly people (aged 76-102 years) did not decrease at 22 weeks after vaccination. This approach confers long-lasting antibody responses and may be useful in clinical practice.

Hemagglutination inhibiting antibody persistence 1 year after influenza vaccination in Korean children and adolescents.

This study aimed to assess the 1-y immunogenicity of influenza vaccines and the association between immunogenicity at 1 m and further influenza infections in children aged 6 m to 18 y. Serum hemagglutination inhibition (HI) antibody titers and GMTs were determined for the recommended influenza strains 0, 1, 6, and 12 m post-vaccination. The serological evidence of influenza infections were defined as the increase of HI titer (HI ≥1:40 and 4-fold rise). The seroprotection rates for strains A(H1N1), A(H3N2), and B were 91.2%, 87.6%, and 87.6%, respectively, at 1 month (n = 174). These rates were 76.5%, 64.7%, and 54.6%, respectively, at 12 m. The seroprotection rates and GMTs for influenza A(H1N1) and A(H3N2) were higher at 12 m than at 0 m (p < 0.05) but not for B. There were 39 subjects (42 cases) of serological influenza infections. Subjects with seroprotection at 1 m post-vaccination had showed fewer serologic A(H1N1) (10.1 vs 54.5%) and A(H3N2) (7.2 vs 38.1%) infections than the ones with HI titer <1:40 during follow-up (P < 0.01). In conclusion, influenza vaccines used during the 2008-09 season induced adequate 1-y immunogenicity for A(H1N1) and A(H3N2). The immunogenicity at one month after vaccination influenced further serological influenza infections.

Persistence of immunity in healthy adults aged ≥ 50 years primed with a hepatitis B vaccine 3 years previously.

Hepatitis B vaccines do not generate protective immune responses in older adults as effectively as they do in children and young adults. Improved formulations of existing vaccines may have the potential to improve this. This study investigated the persistence of serum antibodies against hepatitis B surface antigens (anti-HBs) 3.1-3.5 years following primary vaccination with 3 doses of HBvaxPRO® or Engerix B™ in healthy adults aged ≥ 50 years who were further challenged with 1 dose of recombinant hepatitis B antigen. This was an open-label extension study. Individuals (N = 204) with a mean (standard deviation) age at enrollment of 63.7 (7.0) years receiving HBvaxPRO® or Engerix B™ in a randomized, double-blind primary study were challenged with 1 dose of HBvaxPRO® (10 µg). Anti-HBs were measured pre- and 30 days post-challenge. 45.5% (34.8, 56.4 [95% CI]) of individuals who received HBvaxPRO® in the per protocol set (PPS) had anti-HBs titers ≥ 10 mIU/mL pre-challenge and 85.2% (76.1, 91.9) 1-month post-challenge. In those who received Engerix B™ in the primary vaccination series, the results were 58.8% (48.6, 68.5) and 88.3% (80.5, 93.8), respectively. The challenge dose of HBvaxPRO® was generally well tolerated. Subjects aged ≥ 50 years receiving a challenge dose of HBvaxPRO® demonstrated immune memory against hepatitis B 3 years after a 3-dose primary. The safety profile of this challenge dose of HBvaxPRO® was consistent with the well-established safety profile of the vaccine HBvaxPRO®.

Cost-effectiveness of hepatitis B vaccination using HEPLISAV™ in selected adult populations compared to Engerix-B® vaccine.

OBJECTIVE: HEPLISAV™ is an adult hepatitis B vaccine that requires fewer doses over a shorter period of time and elicits higher and earlier seroprotection compared to Engerix-B to reduce the risk of hepatitis B infection. The objective of this analysis was to evaluate the cost-effectiveness of vaccination with HEPLISAV vs. Engerix-B(®) to prevent hepatitis B infection in select populations. METHODS: Markov models were developed for the following populations: diabetics, patients with chronic or end stage kidney disease, healthcare workers and international travelers to countries with high HBV infection prevalence. Hepatitis B disease progression was modeled using 11 health states: seroprotected, susceptible, acute infection, chronic infection, fulminant hepatic failure, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplant, post-transplant care, and death. Seroprotection rates were obtained from two phase 3 clinical trials comparing HEPLISAV with Engerix-B and ranged across various populations from 89-96% for HEPLISAV and 62-81% for Engerix-B. Higher vaccination completion rates were assumed for HEPLISAV compared with Engerix-B given that fewer doses of HEPLISAV are required in a shorter period of time to achieve seroprotection for the evaluated populations. Each cycle length after the first year in the model was 1-year. All future costs and benefits were discounted at 3%. A lifetime analysis and a U.S. payer perspective were used. RESULTS: HEPLISAV has a favorable cost-effectiveness profile with incremental cost effectiveness ratios <$25,000 across all populations studied. In the patients with chronic or end stage kidney disease, HEPLISAV was the dominant option and was cost-saving compared with Engerix-B. The cost of vaccine, regimen completion rates, and seroprotection rates were the sensitive variables in the models. CONCLUSIONS: HEPLISAV is a cost-effective option to provide high rates of seroprotection and early seroprotection across a range of populations from health care workers to patients with chronic or end stage kidney disease.

Long-term immunogenicity of an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in young and elderly adults: an observer-blind, randomized trial.

BACKGROUND: This study (NCT00979602) evaluated the immunogenicity and relative protective efficacy of one dose of influenza A(H1N1)pdm09 vaccine with or without AS03 (an α-tocopherol oil-in-water emulsion based Adjuvant System). METHODS: Four thousands and forty-eight healthy adults aged ≥ 18 years were randomized (1:1) to receive one dose of either the adjuvanted split virion (3.75 µg hemagglutinin antigen [HA]/AS03) or non-adjuvanted (15 µg HA) vaccine. Hemagglutination inhibition [HI] antibody response was evaluated before vaccination and at Days 21, 42 and 182 (Month 6). Safety of the study vaccines was evaluated during the entire study duration. RESULTS: At Day 21, both study vaccines induced HI immune responses meeting the US regulatory criteria in subjects 18-64 years (seroprotection rate [SPR]: 98.0% [97.1-98.6]; seroconversion rate [SCR]: 89.7% [88.0-91.2] in the AS03-adjuvanted group; SPR: 91.4% [89.9-92.8]; SCR: 74.6% [72.3-76.9] in the non-adjuvanted group) and >64 years of age (SPR: 86.0% [82.5-89.0]; SCR: 75.3% [71.1-79.2] in the AS03-adjuvanted group; SPR: 69.1% [64.6-73.3]; SCR: 56.7% [52.0-61.3] in the non-adjuvanted group). The AS03-adjuvanted vaccine induced higher HI geometric mean titers than the non-adjuvanted vaccine at all time points. At Month 6, only subjects 18-64 years of age from both vaccine groups still met the US regulatory criteria (SPR: 82.1% [80.0-84.1]; SCR: 62.3% [59.6-64.8] in the AS03-adjuvanted group; SPR: 75.3% [72.9-77.5]; SCR: 53.7% [51.0-56.4] in the non-adjuvanted group). Protective efficacy was not evaluated due to low number of RT-qPCR-confirmed A(H1N1)pdm09 influenza cases. Through Month 12, 216 serious adverse events (in 157 subjects: 84 in the AS03-adjuvanted and 73 in the non-adjuvanted group) and 12 potentially immune mediated diseases (5 in the AS03-adjuvanted and 7 in the non-adjuvanted group) were reported. CONCLUSION: A single dose of either adjuvanted or non-adjuvanted influenza A(H1N1)pdm09 vaccine induced protective HI antibody levels against the A/California/7/2009 strain that persisted through Month 6 in the 18-64 years population.

Immune response to 2009 H1N1 vaccine in HIV-infected adults in Northern Thailand.

BACKGROUND: In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza®, Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries. RESULTS: At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8-41.6) and 35.0% (95%CI 15.4-59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05). METHODS: We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer < 1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40. CONCLUSIONS: A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.