Safety and immunogenicity of a booster dose of meningococcal (groups A,C, W,and Y) polysaccharide diphtheria toxoid conjugate vaccine

BackgroundQuadrivalent meningococcal conjugate vaccines (MenACWY) were developed to offer long-term protection against invasive disease caused by serogroups A, C, W, and Y. Reduced MenACWY effectiveness within 5 years after primary vaccination (likely due to declining bactericidal antibody titers) has been described, particularly with respect to C and Y disease in the United States. We evaluated the safety and immunogenicity of a single booster dose of quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) in adolescents and adults who received a previous dose 4–6 years earlier.MethodsThis phase 2, open-label, multicenter study of 834 persons was conducted in the United States. Participants received a single 0.5-mL booster dose of MenACWY-D. Serogroup-specific bactericidal antibody geometric mean titers (GMTs) were measured with a serum bactericidal antibody assay using human complement (hSBA). Proportions of participants achieving antibody titers of ⩾1:8 for each vaccine serogroup on Days 6 and 28 were determined. Rates of adverse events (AEs), including serious adverse events (SAEs), were also assessed.ResultsBefore booster vaccination, 38.7–68.5% of participants had an hSBA titer ⩾1:8, depending on vaccine serogroup. By Day 6 post-vaccination, 98.2–99.1% of participants had hSBA titers ⩾1:8. By Day 28, >99% of participants achieved this threshold and the primary hypothesis (lower limit of the one-sided 95% confidence limit ⩾85% for each serogroup) was met. The GMT ratios (post-vaccination divided by pre-vaccination) at Day 28 ranged from 47.2 (serogroup A) to 209.1 (serogroup Y). Rates of AEs, including SAEs, were similar to those observed among adolescents and adults who received a primary dose of MenACWY-D in previous studies. There were no study discontinuations due to an AE and no deaths.ConclusionsBooster vaccination with MenACWY-D was safe and induced robust bactericidal antibody responses, consistent with immune memory, among adolescents and adults 4–6 years after primary vaccination.ClinicalTrials.gov registration: NCT01442675.     

Meningococcal serogroup C immunogenicity,antibody persistence and memory B-cells induced by the monovalent meningococcal serogroup C versus quadrivalent meningococcal serogroup ACWY conjugate booster vaccine: A randomized controlled trial

BackgroundAdolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster.MethodsHealthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year.ResultsOf 501 participants, 464 (92.6%) were included in the ‘according to protocol’ cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds.ConclusionBoth MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term.     

Factors associated with humoral immune response in older adults who received egg-free influenza vaccine

BackgroundImmune responses to influenza vaccination tend to be lower among older, frequently vaccinated adults. Use of egg-free influenza vaccines is increasing, but limited data exist on factors associated with their immunogenicity in older adults.MethodsCommunity-dwelling older adults ≥ 56 years of age were enrolled in a prospective, observational study of immunogenicity of 2018–2019 influenza vaccine. Hemagglutination inhibition (HAI) antibody titers were measured pre-vaccination (Day 0) and four weeks after vaccination (Day 28) to calculate geometric mean titers, seropositivity (HAI titers ≥ 1:40), seroconversion (fourfold rise in HAI titer with post-vaccination titer ≥ 1:40) and geometric mean fold rise (GMFR). Linear regression models assessed the association of predictors of GMFR for each vaccine antigen.ResultsAmong 91 participants who received egg-free influenza vaccines, 84 (92.3 %) received quadrivalent recombinant influenza vaccine (RIV4, Flublok, Sanofi Pasteur), and 7 (7.7 %) received quadrivalent cell culture-based influenza vaccine (ccIIV4, Flucelvax, Seqirus). Pre-vaccination seropositivity was 52.8 % for A(H1N1), 94.5 % for A(H3N2), 61.5 % for B/Colorado and 48.4 % for B/Phuket. Seroconversion by antigen ranged from 16.5 % for A(H1N1) and B/Colorado to 37.4 % for A(H3N2); 40 participants failed to seroconvert to any antigen. Factors independently associated with higher GMFR in multivariable models included lower pre-vaccination HAI antibody titer for A(H1N1), B/Colorado and B/Phuket, and younger age for A(H1N1).ConclusionOverall pre-vaccination seropositivity was high and just over half of the cohort seroconverted to ≥ 1 vaccine antigen. Antibody responses were highest among participants with lower pre-vaccination titers. Among older adults with high pre-existing antibody titers, approaches to improve immune responses are needed.     

Rubella virus neutralizing antibody response after a third dose of measles-mumps-rubella vaccine in young adults

BackgroundThird doses of measles-mumps-rubella (MMR) vaccine have been administered during mumps outbreaks and in various non-outbreak settings. The immunogenicity of the rubella component has not been evaluated following receipt of a third dose of MMR vaccine.MethodsYoung adults aged 18–31 years with documented two doses of MMR vaccine received a third dose of MMR vaccine between July 2009 and October 2010. Rubella neutralizing antibody titers were assessed before, 1 month, and 1 year after receipt of a third dose of MMR vaccine.ResultsAmong 679 participants, 1.8% had rubella antibody titers less than 10 U/ml, immediately before vaccination, approximately 15 years after receipt of a second dose of MMR vaccine. One month after receipt of a third dose of MMR vaccine, average titers were 4.5 times higher and >50% of participants had a 4-fold boost. Response was highest among those with titers less than 10 U/ml prior to vaccination (geometric mean titer ratio = 18.8; 92% seroconversion) and decreased with increasing pre-vaccination titers. Average titers declined 1 year postvaccination but remained significantly higher than pre-vaccination levels. The proportion classified as low-positive antibody levels increased from 3% 1 month postvaccination to 24% 1 year postvaccination.ConclusionsVaccination with a third dose of MMR vaccine resulted in a robust boosting of rubella neutralizing antibody response that remained elevated 1 year later. Young adults with low rubella titers are more likely to benefit from a third dose of MMR vaccine.     

Superior immunogenicity profile of the new intradermal influenza vaccine compared to the standard subcutaneous vaccine in subjects 65 years and older: A randomized controlled phase III study

BackgroundAlthough the elderly are at high risk for influenza, the immunogenicity in the elderly is lower than that in younger adults. We developed the new type of seasonal influenza vaccine with the novel intradermal (ID) injection system. In the previous exploratory phase I/II study of the ID vaccine with a dose of 15 μg HA per strain showed the superior immunogenicity profile to that of the standard subcutaneous (SC) injection vaccine in subjects aged 20 years and older.MethodsIn this multicenter, randomized, double-blind, active controlled study, 900 adults aged 65 years and older were randomized at an equal ratio to either the ID vaccine group or the licensed standard SC vaccine group. Immunogenicity was assessed using serum hemagglutination inhibition (HAI) titers. The co-primary endpoints were the geometrical mean titers (GMT) and the seroconversion rates (SCR) of HAI titers against 3 vaccine strains on Day 21 (21 days after vaccination). To evaluate the early phase immunogenicity, the GMTs and SCRs on Day 7 were also assessed in the same way as the secondary endpoints.ResultsThe superiority of the ID vaccine in the GMTs and SCRs were demonstrated in all 3 vaccine strains both on Day 7 and Day 21. The frequency of any injection-site reactions was higher in the ID vaccine group, while the severity of injection-site reactions and the frequency of systemic AEs were comparable between the ID and the SC vaccine groups.ConclusionsA single-dose of the influenza vaccine with the novel ID injection system and a dose of 15 μg HA was suggested as an appropriate regimen for clinical use in influenza prevention and associated disease burden reduction. It was also suggested that the new ID vaccine has the potential to replace the standard influenza vaccine from the view point of immunogenicity and safety.Trial registrationJAPIC Clinical Trials Information (JapicCTI-142493).     

A randomized open-label trial of 2-dose or 3-dose pre-exposure rabies prophylaxis among Thai children

BackgroundWorld Health Organization changed the recommendation for pre-exposure rabies prophylaxis from 3-dose to 2-dose regimen in 2018. Given limited data of 2-dose regimens in pediatric population, this study aimed to compare the immunogenicity between 2-dose and 3-dose pre-exposure rabies immunization.MethodsThis study was conducted among healthy children aged 2–12 years. They were randomized to 2-dose vaccination (2D) on days 0 and 28 or 3-dose vaccination (3D) on days 0, 7, and 28. Purified Vero cell rabies vaccine (PVRV-Verorab™) was administered intramuscularly. Rabies virus neutralizing antibody (RVNA) titers were measured at 3 time points: 14-day after complete vaccination, 1-year pre-booster vaccination, and 7-day post-booster dose to mimic scenario of rabies exposure. RVNA titers ≥0.5 IU/ml were considered adequate antibody. T cell specific response to rabies vaccine antigen was measured using the interferon-gamma enzyme linked immunospot assay.ResultsFrom September to October 2017, 107 participants (51% males), 78 in 2D group and 29 in 3D group were enrolled. Median age was 5.8 years (IQR 4.4–7.3). All participants had RVNA titers ≥0.5 IU/ml after primary vaccination [GMT 2D: 18.6 (95%CI 15.9–21.8) and 3D: 16.3 (95%CI 13.2–20.1 IU/ml), p = 0.35]. At 1-year prior to receiving the booster, only 80% of the children in 2D group maintained RVNA titers ≥0.5 IU/ml compared to 100% of the children in 3D group (p = 0.01). However, all participants in both groups had RVNA ≥0.5 IU/ml at 7-day post booster vaccination [GMT 2D: 20.9 (95%CI 17.4–25.3) and 3D: 22.2 (95%CI 15.8–31.4) IU/ml (P = 0.75)]. The median number of IFN-γ secreting cells at 7-day post-booster dose was 98 and 128 SFCs per 10⁶ PBMCs in the 2D and 3D groups, respectively (P = 0.30).ConclusionsTwo-dose primary rabies immunization provided adequate antibody at post primary vaccination and post booster. The results support 2-dose regimen of pre-exposure rabies immunization in the pediatric population.     

Immunogenicity and safety of MenACWY-TT,a meningococcal conjugate vaccine,co-administered with routine childhood vaccine in healthy infants: A phase III,randomized study

BackgroundInvasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants.MethodsIn this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15–18 months; group ACWY3+1); 1+1 (at 6 and 15–18 months; group ACWY1+1) or single-dose at 15–18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15–18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15–18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated.ResultsImmunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15–18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators.ConclusionPrimary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.     

Safety and immunogenicity of a replication-deficient H5N1 influenza virus vaccine lacking NS1

BackgroundTraditional inactivated influenza vaccines are the type of vaccines that were most frequently developed for immunization against the highly pathogenic avian H5N1 influenza virus. However, clinical trials with inactivated influenza vaccines for H5N1 indicated that high doses and at least two immunizations are required for an effective immune response (Nicholson et al., 2001; Treanor, Campbell et al., 2006; Treanor, Schiff et al., 2006; Ehrlich et al., 2008). We investigated the safety and immunogenicity of a live attenuated H5N1 vaccine (delNS1-H5N1) lacking the interferon antagonist nonstructural protein 1 (NS1).MethodsWe conducted a double-blind, placebo-controlled, phase 1 study in healthy adult participants who were randomly assigned at a 2:1 ratio to receive two immunizations of delNS1-H5N1 vaccine at 6.8 log10 50% tissue culture infectious doses (TCID₅₀)/subject or 7.5 log10 TCID₅₀/subject, or placebo.ResultsIntranasal vaccination with the live attenuated delNS1-H5N1 vaccine was safe and well tolerated. The most common adverse events identified were symptoms associated with mild influenza infections, such as increased body temperature (>37.0 °C), pharyngeal erythema, rhinitis and throat irritation, and were reported within 7 days after the first immunization. delNS1-H5N1 was able to induce significant vaccine-specific serum antibody titers even at the lower dose level of 6.8 log10 TCID₅₀/subject. Seroconversion occurred in 75% of study participants after only one immunization with 7.5 log10 TCID₅₀/subject. Vaccine-specific local IgA responses were observed in 41.7% of individuals that showed serum antibody responses after 2nd immunization.ConclusionsWe show that vaccination with a live attenuated H5N1 influenza vaccine lacking NS1 is safe and induces significant levels of vaccine-specific antibodies even after one immunization. The safety and immunogenicity data indicate that delNS1-H5N1 has the potential to fulfil the unmet need for an effective influenza vaccine in pandemic situations. (ClinicalTrials.gov identifier NCT03745274).     

A Japanese study to assess immunogenicity and safety of a typhoid Vi polysaccharide vaccine

BackgroundAlthough typhoid fever is rare in Japan, imported cases have been reported occasionally in travelers returning from endemic areas. To achieve licensing of a typhoid Vi polysaccharide vaccine (Typhim Vi^®) and make it widely available in Japan, this study was conducted at the request of the Japanese Ministry of Health Labor and Welfare to assess the immunogenicity and safety of this vaccine when given as a single dose (the recommended schedule of administration) in a Japanese population.MethodsIn this multi-center, open-label, non-comparative, intervention study performed in Japan, 200 healthy volunteers (188 adults [≥18 years of age], 7 adolescents [12–17 years of age] and 5 children [2–11 years of age]) were administered Typhim Vi^®. Immunogenicity was assessed 28 days after vaccinations using an ELISA method of anti-Vi antibody detection. A 4-fold increase in anti-Vi titer was considered as the threshold for seroconversion for anti-Vi antibodies. Safety was assessed up to 28 days following vaccination.ResultsOverall, 92.0% (95% confidence interval [CI]: 87.3–95.4%) of participants achieved seroconversion 28 days after a single dose of typhoid Vi polysaccharide vaccine. GMTs of Vi antibody titers increased from 6.6 (95% CI: 5.8–7.4) prior to vaccination to 157.3 (95% CI: 135.1–183.2) on Day 28 after vaccination. The geometric mean of individual anti-Vi antibody titer ratios (Day 28/Day 0) was 23.9 (95% CI: 20.3–28.3). There were no immediate adverse events and no adverse events led to the discontinuation of participants from the study. Across all age groups, pain and myalgia were the most frequently reported injection site and systemic reactions, respectively. Most of these reactions were mild in intensity and resolved within 7 days.ConclusionsA single dose of typhoid Vi polysaccharide vaccine, Typhim Vi^®, demonstrated good safety and immunogenicity profile in a Japanese population.     

Safety and immunogenicity of a plant-derived recombinant protective antigen (rPA)-based vaccine against Bacillus anthracis: A Phase 1 dose-escalation study in healthy adults

BackgroundThe potential use of Bacillus anthracis as a bioterrorism weapon requires a safe and effective vaccine that can be immediately distributed for mass vaccination. Protective antigen (PA), a principal component of virulence factors edema toxin and lethal toxin of B. anthracis, has been the topic of extensive research. Previously, full-length PA (PA83) was manufactured using a transient plant-based expression system. Immunization with this PA83 antigen formulated with Alhydrogel® adjuvant elicited strong neutralizing immune responses in mice and rabbits and protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. This Phase 1 study evaluates this vaccine’s safety and immunogenicity in healthy human volunteers.MethodsThis first-in-human, single-blind, Phase 1 study was performed at a single center to investigate the safety, reactogenicity, and immunogenicity of the plant-derived PA83-FhCMB vaccine at four escalating dose levels (12.5, 25, 50 or 100 µg) with Alhydrogel® in healthy adults 18–49 years of age (inclusive). Recipients received three doses of vaccine intramuscularly at 28-day intervals. Safety was evaluated on days 3, 7, and 14 following vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) and a toxin neutralizing antibody (TNA) assay on days 0, 14, 28, 56, 84, and 180.ResultsAll four-dose ranges were safe and immunogenic, with no related serious adverse events observed. Peak ELISA Geometric Mean Concentration (GMC) and TNA ED₅₀ Geometric Mean Titer (GMT) were noted at Day 84, 1 month after the final dose, with the most robust response detected in the highest dose group. Antibody responses decreased by Day 180 across all dose groups. Long-term immunogenicity data beyond six months was not collected.ConclusionsThis is the first study demonstrating a plant-derived subunit anthrax vaccine’s safety and immunogenicity in healthy adults. The results support further clinical investigation of the PA83-FhCMB vaccine.ClinicalTrials.gov identifier.NCT02239172.     

Interchangeability of two Enterovirus 71 inactivated vaccines in Chinese children: A phase IV,open-label,and randomized controlled trial

BackgroundIn China, three inactivated Enterovirus 71 (EV71) vaccines have been approved. Although the vaccines in an immunization series should be from a single manufacture, children sometimes have to receive EV71 vaccines from more than one manufacturers. The aim of this study was to evaluate the interchangeability and safety of vaccination with EV71 vaccines from two manufacturers among Chinese children.MethodsWe conducted an open label and randomized controlled study among children aged 6–35 months from November 2018 to January 2019. The participants were randomly assigned (1:1:1:1) to receive EV71 vaccines in one of the four different schedules (two using a single vaccine for all doses from one manufacture, and two mixed schedules using vaccines from two manufactures). Blood samples were collected pre-vaccination (Day 0) and one month after the second dose (Day 60) for neutralizing antibody assay. Immunogenicity was assessed in the per-protocol cohort and safety was assessed in the total vaccinated cohort.ResultsA total of 300 children were enrolled and randomized, of whom 89.0% (267/300) were included in the per-protocol cohort for immunogenicity analysis. The seroconversion rates of the EV71 neutralizing antibody in four groups ranged from 98.4% to 100.0%, and were not significantly different among the groups. Compared with other groups, geometric mean titer was higher in group D, in which the participants received Institute of Medical Biology Chinese Academy of Medical Sciences (CAMS) vaccine in the first dose and the Sinovac vaccine in the second dose. Safety profiles were similar among the four groups and no serious adverse events related to the vaccination were reported.ConclusionsInterchangeability of EV71 vaccines from two manufactures to complete an immunization series showed good immunogenicity and safety. The antibody response levels may vary by vaccination sequences of EV71 vaccines from the two manufacturers.Trial registration: ClinicalTrials.govNCT03873740.     

Immunogenicity of meningococcal polysaccharide conjugate vaccine as a replacement for meningococcal polysaccharide vaccine in children in Guangzhou,China

To assess the durability of antibody persistence after substitution of the MPCV vaccine for the MPSV-A vaccine in children, an observational study was conducted in children who voluntarily received two doses of MPCV-AC instead of MPSV-A between March 2017 and March 2018 in Guangzhou, China. In total, 131 and 47 participants were enrolled in the 3-year-old and 6-year-old groups, respectively. In the 3-year-old group, the seroprotection rate and GMT values for Men A and Men C were raised significantly after 1-month post- dose 1 MPSV booster vaccination. All immune indicators were significantly lower in pre- dose 1 MPSV booster vaccination in the 3-year-old group than after pre- dose 2 MPSV booster vaccination in the 6-year-old group. While no significant differences were found in most immune indicators between the 1-month post- dose 1 MPSV booster vaccination in the 3-year-old group and pre- dose 2 MPSV booster vaccination in 6-year-old group. The substitute meningococcal immunization schedule showed a good immunogenicity in young children, and good sequential immunogenicity with MPSV booster immunization.     

A Phase II,randomized, immunogenicity and safety study of a quadrivalent meningococcal conjugate vaccine,MenACYW-TT,in healthy adolescents in the United States

BackgroundMenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine intended for use in individuals ≥6 weeks of age. We evaluated the safety and immunogenicity of MenACYW-TT when compared to a licensed quadrivalent conjugate meningococcal vaccine (Menveo®; MCV4-CRM; GlaxoSmithKline, Italy), and when co-administered with tetanus, diphtheria, acellular pertussis (Tdap) and human papilloma virus (HPV4) vaccines in healthy meningococcal vaccine-naïve adolescents (10–17 years old) in the United States of America.MethodsIn this pivotal Phase II, open-label, multicenter study, 1715 participants were randomized to receive MenACYW-TT, MCV4-CRM, MenACYW-TT co-administered with Tdap and HPV4, or Tdap and HPV4 vaccines alone (NCT02199691).The primary objective was to evaluate whether antibody responses to MenACYW-TT antigens were non-inferior to antibody responses after MCV4-CRM administration. Meningococcal antibody titers were determined using human complement serum bactericidal assay (hSBA) with titers measured at baseline, and 30 days post vaccination (D30). A vaccine seroresponse was defined as baseline titers <1:8 with post-vaccination titers ≥1:8 or baseline titers ≥1:8 with a ≥4-fold increase at post-vaccination. Safety data were collected up to six months post-vaccination.ResultsNon-inferiority was demonstrated for MenACYW-TT vs MCV4-CRM (primary endpoint), and for MenACYW-TT co-administered with Tdap and HPV4 vs MenACYW-TT alone (secondary endpoint). The vaccine seroresponse rate was higher with MenACYW-TT than with MCV4-CRM, for each serogroup: A: 75.6% vs 66.4%; C: 97.2% vs 72.6%; W: 86.2% vs 66.6%; Y: 97.0% vs 80.8%. The safety profiles of MenACYW-TT, MCV4-CRM, and Tdap and HPV4 vaccines, administered with or without MenACYW-TT, were comparable. There were no vaccine-related serious adverse events.ConclusionsThe MenACYW-TT vaccine was well tolerated and generated an immune response that was non-inferior to the licensed MCV4-CRM vaccine. Immunogenicity and safety profiles were comparable when MenACYW-TT was administered with or without Tdap and HPV4 vaccines in meningococcal vaccine-naïve adolescents.     

Immunogenicity of influenza vaccines administered to pregnant women in randomized clinical trials in Mali and South Africa

BackgroundA key consideration for expanding recommendations for influenza vaccination is a robust assessment of immunogenicity and efficiency of transplacental antibody transfer after maternal vaccination.MethodsWe pooled data from two trials of maternal influenza vaccination to analyze vaccine immunogenicity with more power than either trial had alone. We compared hemagglutination-inhibition (HAI) titers and titer factor change for women and their infants between trial arms using t-tests; maternal and infant putative seroprotective titers (HAI ≥ 1:40) within each trial arm and maternal seroconversion between trial arms using exact tests; and transplacental antibody transfer between trial arms using t-tests. We used marginal linear models and generalized estimating equations to examine the impact of time between maternal vaccination and delivery on transplacental antibody transfer, infant titers, and infant seroprotection.ResultsFor all vaccine components (A/H1N1, A/H3N2, and Type B), >80% of vaccinated women had seroprotective titers, >60% of them seroconverted, and >50% of their infants were born with seroprotective titers. These immunogenicity outcomes occurred more often in vaccine recipients and their infants than in controls. No difference in efficiency of transplacental antibody transfer was observed between vaccine recipients and controls.ConclusionsOur results provide robust support for further expansion of maternal influenza vaccination recommendations.Clinical Trials Registration: NCT01430689 and NCT01306669.     

A+C群脑膜炎球菌多糖疫苗接种反应与血清学观察

目的观察国产A C脑膜炎多糖疫苗(A C疫苗)的接种反应和免疫原性。方法以A C疫苗为观察苗、伤寒Vi多糖疫苗(Vi疫苗)为对照苗,采样用整群随机对照的临床试验方法,确定观察人群和对照人群。在已接种的两组人群中,采取整群分层抽样的方法抽取接种反应观察对象,并进行连续3天随访以观察接种反应。采集部分A C疫苗接种对象免前、免后血标本,检测血清抗体IgG4倍增长情况。结果共随访接种反应观察对象1239人,其中接种流脑A C疫苗的771人、接种伤寒Vi疫苗的468人。A C疫苗接种后第1天局部反应发生率为15.06%,第2天的为0.13%,第3天的为0;接种后第1天全身反应的发生率为1.16%,第2天为0.39%和第3天为0.13%。除接种后第1天A C疫苗的局部反应发生率要明显高于Vi疫苗的外,接种后2天、3天的局部反应和第1、2、3天全身反应的发生率,A C疫苗和Vi疫苗无显著性差异。共采集A C疫苗接种对象免前、免后血标本各100份,抗C群脑膜炎球菌抗体4倍增长率达到94%,抗A群脑膜炎球菌抗体仅达到62%。结论A C疫苗和伤寒Vi多糖疫苗一样,接种反应轻微,安全性好;抗C群脑膜炎球菌抗体免疫应答良好。接种前人群血清抗A群脑膜炎球菌抗体平均浓度比抗C群的高2.6倍,抗A群脑膜炎球菌抗体4倍增长率低可能与本底抗A群脑膜炎球菌抗体水平高有关。     

A live attenuated H5N2 prime- inactivated H5N1 boost vaccination induces influenza virus hemagglutinin stalk specific antibody responses

BackgroundThe emergence and spread of highly pathogenic avian influenza (H5N1) viruses have raised global concerns of a possible human pandemic, spurring efforts towards H5N1 influenza vaccine development and improvements in vaccine administration methods. We previously showed that a prime-boost vaccination strategy induces robust and broadly cross-reactive antibody responses against the hemagglutinin globular head domain. Here, we specifically measure antibodies against the conserved hemagglutinin stem region in serum samples obtained from the prior study to determine whether stalk-reactive antibodies can also be induced by the prime-boost regimen.MethodSerum samples collected from 60 participants before vaccination and on days 7, 28 and 90 following boosting vaccination were used in this study. 40 participants received two doses of live attenuated H5N2 vaccine (LAIV H5N2) followed by one dose of inactivated H5N1 vaccine a year later, while 20 participants received only the inactivated H5N1 vaccine. We tested these serum samples for stalk-reactive antibodies via enzyme-linked immunosorbent (ELISA) and microneutralization assays.ResultsStalk-specific antibody levels measured by both assays were found to be significantly higher in primed individuals than the unprimed group. ELISA results showed that 22.5, 70.5 and 57.5% of primed participants had a four-fold or more increase in stalk antibody titers on days 7, 28 and 90 following boosting vaccination, respectively; whereas the unprimed group had no increase. Peak geometric mean titers (GMT) for stalk antibodies in the LAIV H5N2 experienced group (24,675 [95% CI; 19,531–31,174]) were significantly higher than those who received only the inactivated H5N1 vaccine (8877 [7140–11,035]; p < 0·0001). Moreover, stalk antibodies displaying neutralizing activity also increased in primed participants, but not in the unprimed group.ConclusionOur finding emphasizes the importance of prime-boost vaccination for effectively inducing stalk antibodies, which is an attractive target for developing vaccines that induce stalk reactive antibodies.     

The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines

Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningococcal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines.     

An evaluation of the safety and immunogenicity of MVC-COV1901: Results of an interim analysis of a phase III,parallel group,randomized, double-blind,active-controlled immunobridging study in Paraguay

BackgroundData from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901.MethodsIn this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18–91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses.ResultsA total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non-inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive.ConclusionSafety and immunogenicity data of MVC-COV1901 from the study in Paraguay confirm previous results. The previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown.     

Long-term persistence of protective antibodies in Dutch adolescents following a meningococcal serogroup C tetanus booster vaccination

IntroductionDue to waning immunity, infant vaccination with meningococcal serogroup C conjugated (MenCC) vaccines is insufficient to maintain long-term individual protection. Adolescent booster vaccination is thought to offer direct protection against invasive meningococcal disease (IMD) but also to reduce meningococcal carriage and transmission and in this way establish herd protection in the population. Previously, we studied antibody levels after adolescent MenCC booster vaccination. In the present study, the adolescent vaccinees were revisited after three years to determine antibody persistence and to predict long-term protection.MethodsMeningococcal serogroup C tetanus toxoid conjugated (MenC-TT) vaccine was administered to 10-, 12- and 15-year old participants who had been primed nine years earlier with a single dose of MenC-TT vaccine. Blood samples were collected before, 1 month, 1 year and 3 years after the adolescent booster vaccination. Functional antibody levels were measured with serum bactericidal assay using rabbit complement (rSBA). Meningococcal serogroup C polysaccharide and tetanus toxoid specific antibody levels were measured using fluorescent-bead-based multiplex immunoassay. Long-term protection was estimated using longitudinal multilevel antibody decay modeling.ResultsOf the original 268 participants, 201 (75%) were revisited after 3 years. All participants still had an rSBA titer above the protective threshold of ⩾8 and 98% ⩾128. The 15-year-olds showed the highest antibody titers. Using a bi-exponential decay model, the median time to fall below the protection threshold (rSBA titer <8) was 16.3 years, 45.9 years and around 270 years following the booster for the 10-, 12- and 15-year-olds, respectively.ConclusionsAfter a first steep decline in antibody levels in the first year after the booster, antibody levels slowly declined between one and three years post-booster. A routine MenC-TT booster vaccination for adolescents in the Netherlands will likely provide long-term individual protection and potentially reduce the risk of resurgence of MenC disease in the general population.     

海拉尔铁路工务系统职工接种森林脑炎疫苗免疫效果观察

目的为了解海拉尔铁路工务系统的线路工人接种森林脑炎疫苗后的免疫效果。方法随机抽取工务系统在林业区段作业的402名职工,于预防接种前和接种后三周进行静脉采血,采用酶联免疫法进行抗体检测。结果免疫接种后抗体阳性率为98.76%;免疫前连续接种5年者抗体阳性率高于连续接种3年者、未连续接种者和从未接种者;吸烟、饮酒等不良生活习惯并不影响注射疫苗后抗体的产生。结论长春生物制品研究所研制的这种新型地鼠肾纯化灭活疫苗（森泰保）具有较高的抗体阳转率,但接种疫苗后的抗体水平维持时间较短,需每年进行加强注射才能维持身体内的抗体水平。接种年限越长血清抗体水平越高。吸烟、饮酒不良生活习惯不影响抗体的产生。