Comparison of the safety and immunogenicity of an investigational and a licensed quadrivalent meningococcal conjugate vaccine in children 2-10 years of age

Background

Routine administration of quadrivalent meningococcal conjugate vaccine to adolescents and certain high risk groups is recommended in the United States and Canada. We compared the immunogenicity and safety of an investigational quadrivalent meningococcal vaccine conjugated to CRM-197 (MenACWY-CRM) with a licensed quadrivalent vaccine conjugated to diphtheria toxoid (MCV4) in children aged 2–10 years.

Methods

Eligible 2–5-year-olds were randomized 1:2:2 to receive either 2 doses of MenACWY-CRM, or 1 dose of MenACWY-CRM or MCV4; 6–10-year-olds were randomized 1:1 to receive a single dose of MenACWY-CRM or MCV4. The primary immunogenicity assessment was seroresponse separately for the two age cohorts 28 days following a single dose of MenACWY-CRM or MCV4. Noninferiority and superiority criteria were predefined. Solicited injection-site and systemic reactions were collected for the 7 days postvaccination.

Results

A total of 2907 children were randomized to receive study vaccine. MenACWY-CRM met statistical superiority criteria vs. MCV4 for groups W and Y and was noninferior for group C in both age strata. For group A, noninferiority criteria were not met; the group A seroresponse rates for MenACWY-CRM and MCV4, respectively were 72% (95% confidence interval 68–75%) and 77% (73–80%) in 2–5-year-olds and 77% (73–80%) and 83% (79–86%) in 6–10-year-olds. When the two age strata were combined (2–10-year-old children), MenACWY-CRM was noninferior to MCV4 for all four groups, and statistically superior for groups C, W, and Y. Safety parameters were similar across age cohorts and vaccines groups.

Conclusions

MenACWY-CRM and MCV4 were immunogenic and well tolerated in children aged 2–10 years. Seroresponse to MenACWY-CRM was statistically noninferior to MCV4 for all groups, and statistically superior for groups C, W, and Y.

Trial registration

Clinicaltrials.gov identifier: NCT00616421.     

Chemistry of a new investigational quadrivalent meningococcal conjugate vaccine that is immunogenic at all ages

Meningococcal disease is a serious medical condition that can prove fatal within hours in otherwise healthy individuals. Disease incidence is highest in infants, yet there is no broadly protective quadrivalent vaccine that covers this age group. A new investigational quadrivalent meningococcal glycoconjugate vaccine against meningococcal serogroups A, C, W-135, and Y (MenACWY-CRM, Novartis Vaccines, Siena, Italy), has been developed to meet this medical need. This article discusses the vaccine technology behind MenACWY-CRM, focusing on the heritage of CRM₁₉₇, the conjugation chemistry, the sizing of the oligosaccharides, and the advantages that these may confer on the vaccine. We highlight the differences between available vaccines and look at the clinical experience with vaccines against other diseases, demonstrating the importance of each component to the immunogenicity of conjugate vaccines. The specific technological approach, including conjugation of meningococcal oligosaccharides of defined length to the CRM₁₉₇ protein, has led to a vaccine that has the potential to provide broad meningococcal protection against serogroups A, C, W-135, and Y for all ages.     

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study

BackgroundThe MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks–15 months of age).MethodsFive schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone. Routine pediatric vaccines (DTaP-IPV/Hib, PCV7/PCV13, MMR, and varicella) were administered per approved schedules. Proportions of participants with serum bactericidal antibodyassay with human complement (hSBA) titers ≥1:4 and ≥1:8, SBA with baby rabbit complement (rSBA) titers ≥1:8 and ≥1:128, and immune responses against concomitant vaccines were determined.ResultsTenderness and irritability were the most frequent solicited injection site and systemic reactions. Similar proportions of participants achieved an hSBA titer ≥1:8 for all four serogroups regardless of whether 2 or 3 doses were administered in the first year of life. Following a second-year dose, 91–100% of participants achieved the threshold for all 4 serogroups in all schedules regardless of the number of doses in the first year of life. Similar responses were seen with rSBA. Immunogenicity and safety profile of concomitant vaccines was similar whether the MenACYW-TT conjugate vaccine was administered or not.ConclusionMenACYW-TT conjugate vaccine administered with pediatric vaccines is safe and immunogenic regardless of the schedule and does not affect the immunogenicity or safety of the concomitant vaccines.Clinical trial registryNCT01049035.     

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.     

Adolescent meningococcal serogroup A,W and Y immune responses following immunization with quadrivalent meningococcal A,C, W and Y conjugate vaccine: Optimal age for vaccination

BackgroundRecently the incidence of meningococcal serogroup Y (MenY) and in particular serogroup W (MenW) invasive disease has risen in several European countries, including the Netherlands. Adolescents are a target group for primary prevention through vaccination to protect against disease and reduce carriage and induce herd protection in the population. The present study assessed MenA, MenW and MenY antibody levels in adolescents up to one year following primary vaccination with quadrivalent MenACWY-PS conjugated to tetanus toxoid (MenACWY-TT).MethodsIn this phase IV, open-label study, healthy 10-, 12- and 15-year-olds received the MenACWY-TT vaccine. Blood samples were collected before, 1 month and 1 year after the vaccination. Functional antibody levels against MenA, MenW and MenY were measured with serum bactericidal assay using baby rabbit complement (rSBA). MenA-, MenW-, and MenY-PS specific IgG, IgG1 and IgG2 levels were measured using fluorescent-bead-based multiplex immunoassay.ResultsThe quadrivalent MenACWY-TT vaccine elicited robust antibody responses against MenA, MenW and MenY, and the majority (94%) of the participants maintained rSBA titers ≥128 one year after the vaccination against all three serogroups. After one year, higher MenW rSBA GMTs were observed in the 12- and 15-year-olds compared to the 10-year-olds, while rSBA GMTs against MenA and MenY were similar between age groups. Furthermore, those participant who showed SBA titer ≥8 at baseline, also had higher antibody levels one year after vaccination as compared to participants with rSBA titer <8 at baseline.ConclusionThe MenACWY-TT vaccine induces robust protective primary immune responses up to one year after vaccination. Our results suggest that persistence of individual protection increases with the age at which a primary quadrivalent MenACWY-TT vaccination is administered. Our results indicate that 12 or 15 years seems a more optimal age for a primary quadrivalent MenACWY-TT vaccination to protect against the rapid increase of MenW disease.     

Humoral immune response following the inactivated quadrivalent influenza vaccination among HIV-infected and HIV-uninfected adults

BackgroundA limited amount of information is available about the immunogenicity of the quadrivalent inactivated influenza vaccine among human immunodeficiency virus (HIV)-infected individuals, especially in low and middle-income countries (LMICs).MethodsHIV-infected adults and HIV-uninfected adults received a dose of quadrivalent inactivated influenza vaccine including strains of H1N1, H3N2, BV and BY. Enzyme-linked immunosorbent assay (ELISA) and hemagglutination-inhibition assay (HAI) were used to determine IgA, IgG antibody concentration and geometric mean titers (GMT) at day 0 and day 28, respectively. Associated factors contributing to seroconversion or GMT changes were analyzed using simple logistic regression model.ResultsA total of 131 HIV-infected and 55 HIV-uninfected subjects were included in the study. In both HIV-infected and uninfected arms, IgG and IgA against influenza A and B all increased significantly at day 28 after receiving QIV (P < 0.001). GMTs of post-vaccination at day 28 showed that HIV-infected persons with CD4 + T cell counts ≤ 350 cells/mm³ were statistically less immunogenic to all strains of QIV than HIV-uninfected ones (P < 0.05). HIV-infected participants with CD4 + T cell counts ≤ 350 cells/mm³ were less likely to achieve seroconversion to QIV (H1N1, BY and BV) than HIV-uninfected individuals at day 28 after vaccination (P < 0.05). Compared with HIV-infected patients with baseline CD4 + T cell counts ≤ 350 cells/mm³, individuals with baseline CD4 + T cell counts > 350 cell/mm³ seemed more likely to generate antibody responses to H1N1 (OR:2.65, 95 %CI: 1.07–6.56) and BY (OR: 3.43, 95 %CI: 1.37–8.63), and showed a higher probability of seroconversion to BY (OR: 3.59, 95 %CI: 1.03–12.48). Compared with nadir CD4 + T cell count ≤ 350 cell/mm³, individuals with nadir CD4 + T cell count > 350 cell/mm³ showed a higher probability of seroconversion to H1N1(OR: 3.15, 95 %CI: 1.14–8.73).ConclusionInfluenza vaccination of HIV-infected adults might be effective despite variable antibody responses. HIV-positive populations with CD4 + T cell counts ≤ 350 are less likely to achieve seroconversion. Further vaccination strategies could be developed for those with low CD4 T cell counts.     

Immune response to 13-valent pneumococcal conjugate vaccine with a reduced dosing schedule

Background

The 7-valent pneumococcal conjugate vaccine (PCV7) has demonstrated effectiveness against pneumococcal illnesses when administered as 3 infant doses plus a toddler dose (3+1 schedule) or as an abbreviated schedule of 2 infant doses plus a toddler dose (2+1 schedule). The 13-valent pneumococcal conjugate vaccine (PCV13) is approved and World Health Organization-prequalified for administration in a 2+1 schedule when used as part of routine immunization programs.

Objective

To summarize immunologic responses elicited by PCV13 administered in a 2+1 schedule and following 2 doses in a 3+1 schedule.

Methods

Studies were double-blind, randomized, active-controlled, multicenter studies except the Mexico study (open-label, single-arm). In 2+1 studies, PCV13 was administered at 2, 4, and 12 (UK) or 3, 5, and 11 (Italy) months. In 3+1 studies (Spain and Mexico), assessment was made postdose 2 of the primary series (2, 4, and 6 months). The primary immunogenicity endpoint was the proportion of participants achieving serotype-specific antipolysaccharide immunoglobulin (Ig)G concentrations ≥0.35 μg/mL (i.e., responders) 1 month postdose 2. Pneumococcal IgG geometric mean concentrations (GMCs), opsonophagocytic activity (OPA), and concomitant vaccine responses were assessed.

Results

PCV13 and PCV7 elicited comparable immune responses for the 7 common serotypes after 2 infant doses. The proportion of PCV13 responders postdose 2 was >85% for most of the 7 common and 6 additional serotypes, except common serotypes 6B (27.9–81.4%) and 23F (55.8–77.5%) and additional serotypes 3 (73.8–96.9%) and 6A (79.2–94.4%). Serotypes 6B and 23F elicited lower IgG GMCs postdose 2 compared with other serotypes; all serotypes demonstrated boosting posttoddler dose. All serotypes demonstrated functional activity; >95% of participants achieved OPA levels ≥1:8 postdose 2. Concomitant vaccine responses were similar between PCV13 and PCV7 groups.

Conclusion

Immune responses elicited by PCV13 following 2 infant doses support transition from PCV7 to PCV13 in countries using a 2+1 schedule.Clinical trial registration numbers: UK (Study 007) NCT00384059; Italy (Study 500) NCT00366899; Spain (Study 501) NCT00368966; Spain (Study 3007) NCT00474539; and Mexico (Study 3009) NCT00708682.     

Safety and immunogenicity of one dose of MenACWY-CRM,an investigational quadrivalent meningococcal glycoconjugate vaccine,when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines

This Phase III study evaluates an investigational quadrivalent meningococcal CRM₁₉₇ conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11–18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres ≥1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11–18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.     

乙型肝炎疫苗初次免疫正常应答和高应答婴儿初次免疫5年后免疫记忆持久性随访观察

目的 探讨乙型肝炎(乙肝)疫苗初次免疫(初免)正常应答和高应答新生儿在初免后5年免疫记忆情况及其影响因素。方法 对初免正常应答和高应答新生儿于初免后5年检测其抗-HBs,其中低于保护水平(10 mIU/ml)者接种1剂次乙肝疫苗(激发剂次)并于接种后14 d采集血标本,再次检测抗-HBs,并计算激发剂次后抗-HBs阳转率(≥10 mIU/ml)和GMT。将检测的初免抗体、随访抗体和激发剂次后抗体均从低到高分成不同等级,分析激发剂次后抗体的影响因素。结果 37.98%(980/2 580)初免正常应答和高应答新生儿在初免后5年抗-HBs已降至保护水平以下,其中激发剂次后98.95%(757/765)出现抗体阳转,GMT为2 811.69(95%CI:2 513.55～3 145.19) mIU/ml。激发剂次后抗体滴度随初免抗体水平和随访抗体水平的升高而升高(F值分别为5.46、10.23,均P<0.000 1)。多因素分析显示,激发剂次后抗体滴度与性别、出生体重、早产等无关(P>0.05),而与初免抗体和随访抗体水平独立相关(OR=1.001,95%CI:1.000～1.002,P<0.001;OR=1.28,95%CI:1.81～1.39,P<0.001)。结论 新生儿乙肝疫苗初免后5年存在较强的免疫记忆;免疫记忆的强度与初免抗体及激发剂次前抗体水平有关。     

The effect of an alternative reduced-dose infant schedule and a second year catch-up schedule with 7-valent pneumococcal conjugate vaccine on pneumococcal carriage: a randomized controlled trial

Background

The 7-valent pneumococcal conjugate vaccine (PCV7) was initially licensed for use as 3 infant doses and a booster (3 + 1). However, 2 infant doses plus a booster schedules only (2 + 1) are widely used. We compared the effect of these two schedules on pneumococcal carriage in young children. We also assessed the effect of a 2-dose schedule in the second year (“catch-up” schedule; 0 + 2).

Methods

Subjects (n = 733) were randomized to the 2 + 1 (4, 6, 12 m), 3 + 1 (2, 4, 6, 12 m) or 0 + 2 (12, 18 m) schedules. Blood samples for serotype-specific IgG (SSIgG) determination were obtained at 2, 7, 13, 19 months, and nasopharyngeal + oropharyngeal pneumococcal cultures were obtained at 2, 4, 6, 7, 12, 13, 18, 19, 24, 30 months.

Results

After primary infant PCV7 series, SSIgG was significantly lower for four out of seven serotypes in children receiving 2 doses compared to 3 doses, particularly for serotypes 6B and 23F. This was associated with a higher acquisition and prevalence rates of vaccine serotype carriage in the 2-dose group, particularly serotypes 6A and 6B. After the booster dose at 12 months of age, most differences were not significant anymore. A single PCV7 dose at age 12 months in previously unvaccinated subjects (“catch up” schedule) resulted in poor SSIgG concentrations for three out of seven serotypes, resulting in higher acquisition and prevalence rates of vaccine serotypes (grouped) compared to infants receiving a booster dose at 12 months (2 + 1 and 3 + 1 groups). Similarly, serotypes 6B and 6A also showed significantly higher carriage rates after a single dose at 12 months. After the second catch-up dose at 18 months, the rates were similar to those in the 2 + 1 or 3 + 1 schedules, except for serotype 6A.

Conclusions

Three infant doses seem to better protect against PCV7-serotype acquisition and carriage than two. However, after booster, most of these differences disappear. A 2-dose second year catch-up campaign may enhance the reduction of PCV7-serotype spread in the community.     

Impact of HIV status and vaccination schedule on bacterial nasopharyngeal carriage following infant immunisation with the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in South Africa

BackgroundNasopharyngeal carriage (NPC) of Streptococcus pneumoniae is a precondition for pneumococcal disease and a source of transmission. This trial evaluated NPC of S. pneumoniae and other pathogens post-vaccination with the pneumococcal non-typeable Haemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) in human immunodeficiency virus (HIV)-infected (HIV+), HIV-exposed-uninfected (HEU), and HIV-unexposed-uninfected (HUU) South African children.MethodsIn this phase III, open, single‐centre, controlled study (ClinicalTrials.gov: NCT00829010), 484 children were stratified by HIV status: 83 HIV+, 101 HEU, and 300 HUU. HIV+ and HEU children received a 3 + 1 PHiD-CV vaccination schedule: primary vaccination, age 6/10/14 weeks, and booster dose, age 9–10 months. HUU infants were randomised (1:1:1) to 3-dose priming and booster (HUU/3+1); 3-dose priming without booster (HUU/3+0); or 2-dose priming and booster (HUU/2+1). Bacterial NPC was assessed 8 times up to 24–27 months of age.ResultsOverall pneumococcal carriage rates were similar across 3+1 groups irrespective of HIV status; trends towards higher carriage rates in the HIV+ than HEU and HUU/3+1 groups were observed at 24–27 months of age. In HUU children, carriage of any pneumococcal serotype was similar for the three different dosing schedules at all timepoints; carriage of vaccine-type pneumococci tended to be lower at 16–19 months and 24–27 months of age in children who had received a booster dose (HUU/2+1 and HUU/3+1 groups) than in the HUU/3+0 group. Carriage rates of NTHi, Staphylococcus aureus and Moraxella catarrhalis were comparable between all groups.ConclusionsHIV infection or exposure did not seem to alter the effect of PHiD-CV on pneumococcal NPC in children during their first 2 years of life. NPC prevalence of vaccine-type pneumococci following vaccination series tended to be lower in children who had received a booster dose in comparison to those who had not.     

Effect of Tdap upon antibody response to meningococcal polysaccharide when administered before,with or after the quadrivalent meningococcal TT-conjugate vaccine (coadministered with the 13-valent pneumococcal CRM197-conjugate vaccine) in adult Hajj pilgrims: A randomised controlled trial

Hajj pilgrims are susceptible to several serious infections and are required to receive multiple vaccinations. Polysaccharide-protein conjugate vaccines contain carrier proteins such as tetanus toxoid (TT), diphtheria toxoid or a mutant of diphtheria toxoid (CRM197). These carrier proteins may interact with other conjugate or combination vaccines containing tetanus or diphtheria on concurrent or sequential administration. We examined the immune interaction of separate and concomitant administration of a tetanus/diphtheria/acellular pertussis (Tdap) vaccine with a TT-conjugated quadrivalent meningococcal vaccine (MCV4) (coadministered with 13-valent pneumococcal CRM197-conjugate vaccine [PCV13]) in adult Australian pilgrims before attending Hajj in 2015.We randomly assigned each participant to one of three vaccination schedules. Group 1 received Tdap 3–4 weeks before receiving MCV4 coadministered with PCV13. Group 2 received all three vaccines concomitantly. Group 3 received MCV4 and PCV13 3–4 weeks before Tdap. Blood samples were collected at baseline, at each vaccination visit and 3–4 weeks after vaccination and tested for response to meningococcal serogroups C, W and Y using a serum bactericidal antibody (rSBA) assay with baby rabbit complement, and to diphtheria and tetanus toxoid, measuring IgG antibodies by ELISA. Participants completed symptom diaries after each vaccination. A total of 166 participants aged 18–64 (median 42) years were recruited, of whom 160 completed the study. Compared to the other groups, Group 1 (given Tdap first) had significantly lower proportion of subjects achieving a ≥4-fold rise in rSBA for serogroup W. No difference was detected across the three groups in achieving protection threshold (rSBA ≥8 post vaccination) or SBA geometric mean titre (GMT) post vaccination.Group 3, which was given MCV4/PCV13 first, had high levels of antibody against diphtheria and tetanus than the other groups, when tested prior to receipt of Tdap; Only the anti-tetanus responses remained significantly higher after Tdap administration. No serious adverse events were reported.In conclusion, when multiple vaccination is required for Hajj pilgrims, administering Tdap concurrently with MCV4/PCV13 produces adequate immune responses, and avoids meningococcal immune interference, in the convenience of a single consultation. However, giving Tdap 3–4 weeks after MCV4/PCV13 has the advantage of an enhanced tetanus toxoid response.The trial is Trials Registry (ANZCTR): ACTRN12613000536763.     

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.     

Duration of the immune response to MMR vaccine in children of two age-different groups

A combined vaccine against measles, mumps and rubella (MMR) was administered to both a group of children aged 10–12 months simultaneously with booster doses of compulsory diphtheriatetanus toxoids and oral poliovirus vaccine and a group of children aged 15–24 months who had previously received booster doses of the compulsory vaccines.Apart from one subject belonging to the second group who was non responder and one from the same group who did not seroconvert against the mumps virus alone, 5 to 6 weeks after MMR vaccine administration we found protective levels of antibodies against measles, mumps and rubella viruses in all children. The follow up of both groups at 3 years did not reveal difference between the two groups. Protective levels of serum antibodies against measles and mumps were found in the two groups, altough a significant decline of rubella antibodies was shown (p < 0.05).Since the immunogenicity of the vaccines in the two groups did not differ, we recommend that the scientific community reconsider the vaccination schedule until now recommended. In our opinion the MMR vaccine should be administered simultaneously with booster doses of diphtheria-tetanus toxoids and oral poliovirus vaccine at 10–12 months of age because this policy improves parents' compliance, markedly reduces community costs and simplifies routine immunization schedule.     

Effect of Tdap when administered before,with or after the 13-valent pneumococcal conjugate vaccine (coadministered with the quadrivalent meningococcal conjugate vaccine) in adults: A randomised controlled trial

Sequential or co-administration of vaccines has potential to alter the immune response to any of the antigens. Existing literature suggests that prior immunisation of tetanus/diphtheria-containing vaccines can either enhance or suppress immune response to conjugate pneumococcal or meningococcal vaccines. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage 2014. We also investigated tolerability of these vaccines separately and concomitantly. We randomly assigned each participant to one of three vaccination schedules. Group A received adult tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3–4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) and CRM197-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines on one day. Group C received PCV13 and MCV4 3–4 weeks before Tdap. Blood samples collected at baseline, each vaccination visit and 3–4 weeks after vaccination were tested using the pneumococcal opsonophagocytic assay (OPA) and by ELISA for diphtheria and tetanus antibodies. Funding for meningococcal serology was not available. Participants completed symptom diaries after each vaccination. A total of 111 participants aged 18–64 (median 40) years were recruited. No statistically significant difference was detected across the three groups in achieving OPA titre ⩾1:8 post vaccination. However, compared to other groups, Group A had a statistically significant lower number of subjects achieving ⩾4-fold rise in serotype 3, and also significantly lower geometric mean titres (GMTs) to six (of 13) pneumococcal serotypes (3, 5, 18C, 4, 19A and 9V). Group C (given prior PCV13 and MVC4) had statistically significant higher pre-Tdap geometric mean concentration (GMC) of anti-diphtheria IgG; however, there was no difference across the three groups following Tdap. Anti-tetanus IgG GMCs were similar across the groups before and after Tdap. No serious adverse events were reported. In conclusion, Tdap vaccination 3–4 weeks before concomitant administration of PCV13 and MCV4 significantly reduced the antibody response to six of the 13 pneumococcal serotypes in adults.The trial is registered at the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12613000536763.     

Safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine coadministered with quadrivalent influenza vaccine: A phase 3 randomized trial

IntroductionOlder adults are at increased risk of adverse outcomes from pneumococcal disease and influenza infections. Vaccination is an established strategy for preventing both illnesses. This study evaluated coadministration of 20-valent pneumococcal conjugate vaccine (PCV20) and an adjuvanted quadrivalent inactivated influenza vaccine (QIV).MethodsThis phase 3, randomized, double-blind, multicenter study included 1796 US adults ≥ 65 years of age randomized 1:1 to receive either PCV20 and QIV followed 1 month later by saline (Coadministration group) or QIV and saline followed 1 month later by PCV20 (Separate Administration group). Primary immunogenicity objectives were to show noninferiority of PCV20 and QIV coadministration compared with separate administration of either vaccine based on serotype-specific opsonophagocytic activity (OPA) titers for PCV20 and strain-specific hemagglutination inhibition assay (HAI) titers for QIV. Safety endpoints included local reactions, systemic events, and adverse events (AEs).ResultsNoninferiority for pneumococcal and influenza antibody responses (lower bound 95 % CI of the OPA and HAI geometric mean ratios of > 0.5 and > 0.67, respectively) was shown for the Coadministration group compared with the Separate Administration group for all 20 pneumococcal serotypes and all 4 influenza vaccine strains. Local reactions and systemic events were mostly mild or moderate in severity across groups; injection site pain was the most frequent local reaction, and fatigue was the most frequent systemic event. Mild and moderate fatigue were reported more frequently after PCV20 and QIV coadministration compared with separate administration (mild, 20.0 % vs 10.8 %-12.6 %; moderate, 12.3 % vs 8.4 %-9.6 %); this was not considered clinically significant. AE reporting rates were similar across groups, and no serious AEs were considered vaccination-related.ConclusionsImmune responses after coadministration of PCV20 and QIV were noninferior to separate administration of either vaccine. The PCV20 safety profile was similar when given together with or after QIV. These findings support PCV20 and QIV coadministration.Trial Registration: ClinicalTrials.gov, NCT04526574.     

双价肾综合征出血热疫苗人群接种反应与免疫学效果观察

观察HFRS沙鼠肾细胞灭活疫苗对非疫区人群的接种反应与免疫学效果。方法：进行荧光抗体及中和抗体检测。结果：疫苗接种1～3针后，轻度体温反应率分别为2.50％、0．63％、1．25％；轻度红肿反应率分别为0.00％、1.88％、1．25％；648名接种者均无严重反应和异常反应。全程接种后2周，荧光抗体阳转率为100％（83／83）；中和抗体总阳转率亦为100％（53／53），其中Ⅰ型为86．8％（46／53），Ⅱ型为962％（51／53）。结论：（1）该疫苗副反应轻，副反应率低，安全性好；（2）免疫效果良好。     

Ten years of experience with the pneumococcal conjugate 7-valent vaccine in children

In children, pneumococcus became the predominant infectious agent, after the routine use of the Hib conjugate vaccine dramatically decreased Haemophilus Influenzae type b prevalence. The incidence of invasive pneumococcal infections (IPI) and of non-invasive infections due to vaccine serotypes (VS) decreased by 80% in Europe along with a 30–40% decrease in the global incidence of IPI in this age group, after the implementation of Prevenar 7^® routine immunization in children below 2 years of age. The decrease of IPI due to VS in other age groups was an indirect benefit. The moderate increase of non-vaccinal serotype IPI incidence did not impede the benefit of the overall program. Serotype 19A was the most frequent and carried resistance to antibiotics. Prevenar 13^®, a second-generation vaccine with six new serotypes, replaced Prevenar 7^® in most countries after 2010, with available evidence of its effectiveness (United Kingdom, US, France).     

肺炎球菌结合疫苗两种免疫效果评价方法的比较分析

目的研究肺炎球菌结合疫苗诱导的功能抗体滴度与总抗体浓度的相关性。方法采用调理吞噬实验(opsonophagocytic assay,OPA)和酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)对13价肺炎球菌结合疫苗免疫后血清样本进行OPA滴度和抗体浓度检测,并就两种检测结果进行比较,分析二者相关性。结果血清型1,3,5,6A,6B,9V,14,18C,19A和23F两种检测结果的相关系数较高,为0.71~0.88。19F和4型的相关系数相对略低,分别为0.66和0.52。结论 OPA法与ELISA法测定的血清抗体效价的相关性较高,二者结果具有良好的一致性。