Sustained efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7.3 years in young adult women

We report efficacy and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine up to 7.3 years post-vaccination. The study was conducted in a population (N = 433) of women enrolled in Brazilian centres from an initial placebo-controlled study. Women were aged 15–25 years at first vaccination. During the most recent year of follow-up, approximately 7 years after initial vaccination, no cases of infection or cytohistological lesions associated with HPV-16/18 were observed in the vaccinees. Vaccine efficacy (95% confidence interval) up to 7.3 years was 94.5% (82.9, 98.9) for incident infection, 100% (55.7, 100) for 12-month persistent infection and 100% (−129.8, 100) for cervical intraepithelial neoplasia grade 2+. Antibody titres for total IgG and neutralising antibodies remained several folds above natural infection levels and ≥96% of women were seropositive. Vaccine safety was similar to placebo. This is the longest follow-up study for a licensed cervical cancer vaccine.     

Safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-positive women in South Africa: A partially-blind randomised placebo-controlled study

In developing countries, risk of human papillomavirus (HPV) infection may be increased by the high prevalence of human immunodeficiency virus (HIV) infection. We evaluated the safety and immunogenicity of the HPV-16/18 AS04-adjuvanted vaccine in HIV-infected women in South Africa. Asymptomatic HIV-positive women aged 18–25 years (N = 120) were stratified by CD4⁺ T-cell count and randomised (1:1) to receive HPV-16/18 vaccine (Cervarix^®; GlaxoSmithKline Vaccines) or placebo (Al[OH]₃) at 0, 1 and 6 months (double-blind). HIV-negative women (N = 30) received HPV-16/18 vaccine (open label). Anti-HPV-16/18 antibody and CD4⁺ T-cell responses, CD4⁺ T-cell count, HIV viral load, HIV clinical stage and safety were evaluated for 12 months. The safety and reactogenicity profile of the HPV-16/18 vaccine was comparable in HIV-positive and HIV-negative women. Irrespective of baseline HPV status, all HIV-positive and HIV-negative women who received the HPV-16/18 vaccine were seropositive for both HPV-16 and HPV-18 after the second vaccine dose (month 2) and remained seropositive for both antigens at month 12. Anti-HPV-16/18 antibody titres at month 12 remained substantially above levels associated with natural infection. The HPV-16/18 vaccine induced sustained anti-HPV-16/18 CD4⁺ T-cell responses in both HIV-positive and HIV-negative women. No impact of baseline CD4⁺ T-cell count or HIV viral load was observed on the magnitude of the immune response in HIV-positive women. In HIV-positive women, CD4⁺ T-cell count, HIV viral load and HIV clinical stage were unaffected by HPV-16/18 vaccine administration. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine appears immunogenic and well-tolerated in women with HIV infection.     

Co-administration of human papillomavirus-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine: randomized study in healthy girls

Background

To evaluate co-administration of GlaxoSmithKline Biologicals’ human papillomavirus-16/18 AS04-adjuvanted vaccine (HPV) and hepatitis B vaccine (HepB).

Methods

This was a randomized, controlled, open, multicenter study. Healthy girls, aged 9-15 years, were randomized to receive HPV (n = 247), HepB (n = 247) or HPV co-administered with HepB (HPV + HepB; n = 247) at Months 0, 1 and 6. Antibodies against hepatitis B surface antigen (HBs), HPV-16 and HPV-18 were measured, and reactogenicity and safety monitored. Co-primary objectives were to demonstrate non-inferiority of hepatitis B and HPV-16/18 immune responses at Month 7 for co-administered vaccines, compared with vaccines administered alone, in the according-to-protocol cohort.

Results

The pre-defined criteria for non-inferiority were met for all co-primary immunogenicity endpoints at Month 7. Anti-HBs seroprotection rates ≥10 mIU/mL were achieved by 97.9% and 100% of girls, respectively, following co-administration or HepB alone. Anti-HBs geometric mean titers (GMTs) (95% confidence interval) were 1280.9 (973.3-1685.7) and 3107.7 (2473.1-3905.1) milli-international units/mL, respectively. Anti-HPV-16 and -18 seroconversion rates were achieved by ≥99% of girls following co-administration or HPV alone. Anti-HPV-16 GMTs were 19819.8 (16856.9-23303.6) and 21712.6 (19460.2-24225.6) ELISA units (ELU)/mL, respectively. Anti-HPV-18 GMTs were 8835.1 (7636.3-10222.1) and 8838.6 (7948.5-9828.4) ELU/mL, respectively. Co-administration was generally well tolerated.

Conclusions

The study results support the co-administration of HPV-16/18 AS04-adjuvanted vaccine with hepatitis B vaccine in adolescent girls aged 9-15 years.

Clinical trials registration

ClinicalTrials.gov registration number NCT00652938.     

Impact of malaria and helminth infections on immunogenicity of the human papillomavirus-16/18 AS04-adjuvanted vaccine in Tanzania

Background

Endemic malaria and helminth infections in sub-Saharan Africa can act as immunological modulators and impact responses to standard immunizations. We conducted a cohort study to measure the influence of malaria and helminth infections on the immunogenicity of the bivalent HPV-16/18 vaccine.

Methods

We evaluated the association between malaria and helminth infections, and HPV-16/18 antibody responses among 298 Tanzanian females aged 10–25 years enrolled in a randomized controlled trial of the HPV-16/18 vaccine. Malaria parasitaemia was diagnosed by examination of blood smears, and helminth infections were diagnosed by examination of urine and stool samples, respectively. Geometric mean antibody titres (GMT) against HPV-16/18 antibodies were measured by enzyme-linked immunosorbent assay.

Results

Parasitic infections were common; one-third (30.4%) of participants had a helminth infection and 10.2% had malaria parasitaemia. Overall, the vaccine induced high HPV-16/18 GMTs, and there was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria. There was some evidence that participants with malaria had increased GMTs compared to those without malaria.

Conclusions

The data show high HPV immunogenicity regardless of the presence of malaria and helminth infections. The mechanism and significance for the increase in GMT in those with malaria is unknown.     

Immune responses elicited by a fourth dose of the HPV-16/18 AS04-adjuvanted vaccine in previously vaccinated adult women

Background

Vaccines are now available for the prevention of HPV-16/18-related cervical infections and pre-cancers, primarily targeting adolescent girls. Since the risk of HPV exposure potentially persists throughout a woman's sexual life, vaccine-derived immunity should be long-term. The current study, HPV-024 (NCT00546078, http://clinicaltrials.gov), assessed the immune memory in North American women who received three doses of HPV-16/18 AS04-adjuvanted vaccine 7 years earlier in HPV-001 (NCT00689741).

Methods

Women vaccinated in HPV-001 received a 4th-dose of the HPV-16/18 vaccine (024-4DV group, N = 65). Post 4th-dose immune responses were compared with post 1st-dose immune responses in cross-vaccination controls (024-3DV group, N = 50). Reactogenicity was compared between the 4th-dose and the 1st-dose administration.

Results

Pre 4th-dose, 100% of subjects in the 024-4DV group remained seropositive for anti-HPV-16/18 antibodies (ELISA). Compared to pre 4th-dose, GMTs for anti-HPV-16 and anti-HPV-18 antibodies were respectively 9.3-fold and 8.7-fold higher at day 7, and 22.7-fold and 17.2-fold higher at month 1. Compared to post 1st-dose, GMTs for anti-HPV-16 and anti-HPV-18 were respectively 80.5-fold and 205.4-fold higher at day 7, and 11.8-fold and 20.5-fold higher at month 1. Furthermore, 68.2% and 77.3% of women had HPV-16/18 specific memory B-cells, respectively, pre 4th-dose, rising to 100% one month post 4th-dose vaccination. The 4th-dose was generally well tolerated.

Conclusion

A 4th-dose of HPV-16/18 AS04-adjuvanted vaccine triggered a rapid and strong anamnestic response in previously vaccinated women, demonstrating vaccine-induced immune memory.     

Modeling the impact of the difference in cross-protection data between a human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and a human papillomavirus (HPV)-6/11/16/18 vaccine in Canada

Background

Improving life satisfaction (LS) and mental wellbeing (MWB) is important for better public health. Like other health issues, LS and MWB are closely related to deprivation (i.e. lack of resources). Developing public health measures that reduce inequalities in wellbeing requires an understanding of how factors associated with high and low LS and MWB vary with deprivation. Here, we examine such variations and explore which public health measures are likely to improve wellbeing while reducing related inequalities.

Methods

A self-administered questionnaire measuring LS and MWB was used with a cross-sectional sample of adults from the North West of England (n?=?15,228). Within deprivation tertiles, analyses examined how demographics, health status, employment, relationships and behaviours (alcohol, tobacco, physical exercise) were associated with LS and MWB.

Results

Deprivation was strongly related to low LS and MWB with, for instance, 17.1?% of the most deprived tertile having low LS compared to 8.9?% in the most affluent. After controlling for confounders, across all deprivation tertiles, better self-assessed health status and being in a relationship were protective against low LS and MWB. Unemployment increased risks of low LS across all tertiles but only risks of low MWB in the deprived tertile. For this tertile, South Asian ethnicity and higher levels of exercise were protective against low MWB. In the middle tertile retired individuals had a reduced risk of low MWB and an increased chance of high LS even in comparison to those in employment. Alcohol??s impact on LS was limited to the most deprived tertile where heavy drinkers were at most risk of poor outcomes.

Conclusions

In this study, positive outcomes for LS and MWB were strongly associated with lower deprivation and good health status. Public health measures already developed to promote these issues are likely to improve LS and MWB. Efforts to increase engagement in exercise are also likely to have positive impacts, particularly in deprived communities. The development of future initiatives that address LS and MWB must take account of variations in their risk and protective factors at different levels of deprivation.     

Study of the safety and immunogenicity of the synthetic malaria SPf66 vaccine in children aged 1-14 years.

Safety and immunogenicity tests of the SPf66 malaria vaccine have been carried out on a population of children, aged 1 to 14 years, in the town of Tumaco, Colombia. Adverse reactions measured after each vaccination were local and minimal, and observed in only a small percentage of the vaccinated children. One year later, no delayed reaction was evident. The majority of the child population developed high antibody titres against SPf66 and the degree of response did not vary with age. These induced antibodies recognize the native parasite proteins, in particular the molecules from which the amino acid sequence of this vaccine was deduced. These studies demonstrate that the SPf66 vaccine is safe and highly immunogenic for use in children greater than 1 year old.     

Reported adverse events in girls aged 13-16 years after vaccination with the human papillomavirus (HPV)-16/18 vaccine in the Netherlands

In 2009, human papillomavirus (HPV) vaccination was offered to girls born in 1993-1996 in a catch-up campaign, followed in 2010 by the implementation of the vaccination in the National Immunization Programme (NIP) for girls born in 1997. To monitor the tolerability of the 2009 catch-up campaign, we investigated the occurrence of adverse events within 7 days after vaccination with the bivalent HPV vaccine. A total of 6000 girls were asked to participate, including 1500 from each birth cohort from 1993 to 1996. One week after each of the required three successive doses, the participants received by e-mail a Web-based questionnaire focused on local reactions and systemic events. One or more questionnaires were returned by 4248 girls. Any local reaction was reported by 92.1% of the girls after the first dose, 79.4% after the second dose, and 83.3% after the third dose, and 91.7%, 78.7%, and 78.4% reported any systemic event after the three doses, respectively. Pain in the arm was the most frequently reported local reaction, of which 24.0%, 11.7%, and 14.7% was classified as pronounced. Myalgia was the most often reported systemic event. The proportion of local reactions and most systemic events was significantly lower after the second and third dose compared with the first dose (Odds ratio [OR], 0.33-0.76). Older girls reported a higher proportion of adverse events than younger girls. After vaccination with the bivalent HPV vaccine, girls 13-16 years of age reported a high proportion of short-term adverse events. These are maximum estimates and not necessarily caused by the vaccination itself. Although, girls experienced HPV vaccination as painful, no serious or unexpected adverse events were reported. The results of this survey are being communicated to health care workers and the public.     

18岁以上人群接种四价流感病毒灭活疫苗免疫原性和安全性的Meta分析

目的 评价18岁以上人群接种四价流感病毒灭活疫苗(QIV)免疫原性和安全性.方法 检索美国国家医学图书馆数据库、Cochrane协作网图书馆、中国生物医学文献数据库、中国期刊全文数据库和万方全文数据库,将有关比较18岁以上人群接种QIV和三价流感病毒灭活疫苗(TIV)免疫原性和安全性的随机对照试验纳入分析.以接种疫苗21 d后产生的针对H1N1、H3N2、B/Victoria、B/Yamagata四个疫苗株的抗体保护率(SPR)和抗体阳转率(SCR)以及不良反应发生率作为结局指标,合并组间的SPR、SCR和不良反应发生率的相对危险度(RR).结果 共纳入5篇文献.针对B/Yamagata的SPR的RR是1.12(95％ CI:1.02～1.22),SCR的RR是2.11(95％ CI:1.51～2.95).针对B/Victoria的SPR的RR是1.14(95％ CI:1.03～1.25),SCR的RR是1.78(95％ CI:1.24～2.55).接种QIV和TIV(含B/Yamagata)后接种部位疼痛发生率的RR是1.23 (95％ CI:1.05～1.44).结论 18岁以上成人接种QIV不仅可以产生与TIV相似的免疫效果和安全性,而且可以对TIV未包含的乙型流感疫苗株产生较好免疫效果.     

Comparison of the immunogenicity and safety of measles vaccine administered alone or with live, attenuated Japanese encephalitis SA 14-14-2 vaccine in Philippine infants

Japanese encephalitis (JE) virus is a major cause of disease, disability, and death in Asia. An effective, live, attenuated JE vaccine (LJEV) is available; however, its use in routine immunization schedules is hampered by lack of data on concomitant administration with measles vaccine (MV). This study evaluated the immunogenicity and reactogenicity of LJEV and MV when administered at the same or separate study visits in infants younger than 1 year of age. Three groups of healthy infants were randomized to receive LJEV at age of 8 months and MV at 9 months (Group 1; n=100); MV and LJEV together at 9 months (Group 2; n=236); or MV and LJEV at 9 and 10 months, respectively (Group 3; n=235). Blood was obtained 4 weeks after each vaccine administration to determine antibody levels for measles and JE. Reactogenicity was assessed by parental diaries and clinic visits. Four weeks after immunization, measles seroprotection rates (defined as > or =340 mIU/ml) were high and comparable in all three groups and specifically, rates in the combined MV-LJEV (Group 2) were not statistically inferior to those in Group 3 receiving MV separately (96% versus 100%, respectively). Likewise, the LJEV seroprotection rates were high and similar between the three groups. The reactogenicity profiles of the three vaccine schedules were also analogous. LJEV and MV administered together are well tolerated and immunogenic in infants younger than 1 year. These results should facilitate incorporation of LJEV into routine immunization schedules with MV.     

Safety and Immunogenicity of the HPV-16/18 AS04-Adjuvanted Vaccine: A Randomized,Controlled Trial in Adolescent Girls

PurposeImmunization of girls against oncogenic human papillomavirus (HPV) types before sexual debut is important for cervical cancer prevention. This phase III blinded, randomized, controlled trial in adolescent girls assessed safety of the HPV-16/18 AS04-adjuvanted vaccine.MethodsGirls (mean age 12 years) in 12 countries received the HPV-16/18 L1 virus-like particle AS04-adjuvanted vaccine (N = 1,035) or hepatitis A virus vaccine as control (N = 1,032) at 0, 1, and 6 months. The primary objective was to compare the occurrence of serious adverse events (SAEs) between groups. HPV-16 and HPV-18 antibody titers were assessed by enzyme-linked immunosorbent assay post-vaccination.ResultsUp to study month 7, 11 girls in the HPV-16/18 vaccine group reported 14 SAEs and 13 girls in the control group reported 15 SAEs. The difference in SAE incidence between groups was .20% (95% CI, ?.78, 1.20). No SAE in the HPV-16/18 vaccine group was considered related to vaccination or led to withdrawal. The incidence of solicited local and general symptoms up to 7 days post-vaccination was moderately higher with the HPV-16/18 vaccine than with control. The incidence of unsolicited symptoms, new onset of chronic diseases, and medically significant conditions was similar between groups. All girls seroconverted for both antigens after three doses of the HPV-16/18 vaccine; geometric mean titers were 19,882.0 and 8,262.0 EU/mL for anti-HPV-16 and -18 antibodies, respectively, in initially seronegative girls.ConclusionsThe HPV-16/18 AS04-adjuvanted vaccine was generally well tolerated and immunogenic when administered to young adolescent females, the primary target of organized vaccination programs.     

MenACWY-TT is immunogenic when co-administered with Tdap and AS04-HPV16/18 in girls and young women: Results from a phase III randomized trial

BackgroundCo-administration of vaccines in adolescents may improve coverage. We assessed co-administration of quadrivalent meningococcal serogroups A, C, W and Y tetanus toxoid-conjugate vaccine (MenACWY-TT), human papillomavirus 16/18 AS04-adjuvanted vaccine (AS04-HPV16/18) and tetanus-diphtheria-acellular pertussis vaccine (Tdap) in girls and young women.MethodsIn this phase IIIb study (NCT01755689), 1300 healthy 9–25-year-old females were randomized (1:1:1:1:1) to receive: MenACWY-TT at month (M) 0 and AS04-HPV16/18 at M1, M2, M7; MenACWY-TT and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; AS04-HPV16/18 at M0, M1, M6; MenACWY-TT, Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6; Tdap and AS04-HPV16/18 at M0 and AS04-HPV16/18 at M1, M6. Immunogenicity, safety and reactogenicity were evaluated.ResultsImmunogenicity of MenACWY-TT and AS04-HPV16/18 when co-administered was non-inferior to that of the 2 vaccines given separately. Co-administration of MenACWY-TT, AS04-HPV16/18 and Tdap was non-inferior to MenACWY-TT administered alone or to Tdap co-administered with AS04-HPV16/18 in terms of immunogenicity for all vaccine components, except pertussis antigens. Post-vaccination, ≥89.5% of participants reached antibody levels above the pre-specified threshold for all antigens. No safety concerns were identified.ConclusionOur data support co-administration of MenACWY-TT with Tdap and AS04-HPV16/18 vaccines in adolescents.     

MF59-佐剂流感亚单位疫苗在中国老年人中的免疫原性和安全性研究

目的 比较MF59-佐剂流感亚单位疫苗与传统的非佐剂流感亚单位疫苗在老年人中的安全性和免疫原性.方法 采用随机、研究者设盲的对照研究,按照2:1的比例分别给予600名60岁以上老年人接种MF-59佐剂流感亚单位疫苗(复立达TM,简称佐剂流感疫苗)和传统的非佐剂流感亚单位疫苗(爱阁力保(R),简称传统亚单位疫苗),观察接种日和接种后7天内的局部反应和全身反应;使用血凝抑制试验检测接种老年人免疫前后的血凝抑制抗体(HI)滴度,计算基线无免疫保护状态受试者的抗体4倍增长阳转率、免疫后HI抗体达到保护水平(≥1:40)的保护率以及抗体GMT值和增长倍数.比较两者在安全性和免疫原性的差异.结果 两组疫苗的局部反应和全身反应相似,但传统亚单位疫苗组(n=200)中注射部位的硬结相对常见(P＜0.05),而佐剂流感疫苗组(n=400)中注射部位轻度疼痛和发热则相对较常见.对于基线无免疫保护状态的受试者,免疫后针对A/H3N2病毒株的抗体阳转率,佐剂流感疫苗组显著高于传统亚单位疫苗组(P＜0.001);除A/H1N1病毒株外,与基线相比,两组疫苗的保护率均有显著提高,但针对A/H3N2病毒株的保护率方面,佐剂流感疫苗显著高于传统亚单位疫苗(P＜0.001);两组疫苗接种后的GMT均比基线明显增加(P＜0.001),但佐剂流感疫苗组明显高于传统亚单位疫苗组.结论 中国老年人对佐剂流感疫苗耐受性良好,佐剂流感疫苗诱导的免疫原性水平比传统亚单位疫苗高,可使免疫力低下的老年人获益更大.     

Immunogenicity and safety of a tetravalent dengue vaccine and a bivalent HPV vaccine given concomitantly or sequentially in girls aged 9 to 14 years in Mexico

Dengue is endemic in several regions, and the global incidence is increasing. The recombinant, live, attenuated, tetravalent dengue vaccine (CYD-TDV) is recommended for dengue seropositive individuals ≥ 9 years. Human papillomavirus (HPV) vaccination is recommended for girls aged 9–14 years to prevent HPV infection-related cancers. This study assessed the immunogenicity and safety of a bivalent HPV (types 16 and 18) vaccine and CYD-TDV when co-administered concomitantly or sequentially.This was a Phase IIIb, randomized, open-label, multicenter study in girls aged 9–14 years in Mexico (NCT02979535). Participants were randomized 1:1 to receive three doses of CYD-TDV 6 months apart and two doses of bivalent HPV vaccine either concomitantly with, or 1 month before (sequentially), the first 2 CYD-TDV doses. Antibody levels were measured at baseline and 28-days after each vaccine dose for all participants, using an enzyme-linked immunosorbent assay for HPV-16 and HPV-18 antibodies, and a plaque reduction neutralization test for the four dengue serotypes; results are reported only for participants who were seropositive at baseline. Safety was assessed for all randomized participants throughout the study.Of the randomized participants, 305/478 (63.8%) were seropositive for dengue at baseline: 154 in the concomitant group and 151 in the sequential group. After the last HPV vaccine dose, the antibody titers for HPV were comparable in seropositive participants between treatment groups, with between group titer ratios of 0.966 for HPV-16 and 0.999 for HPV-18. After dose 3 of CYD-TDV, antibody titers were comparable for the concomitant and sequential groups across all serotypes, with between-group ratios close to 1 (serotype 1: 0.977; serotype 2: 0.911; serotype 3: 0.921; serotype 4: 0.931).CYD-TDV and a bivalent HPV vaccine administered concomitantly or sequentially in dengue seropositive girls aged 9–14 years elicited comparable immune responses with similar safety profiles.     

Increases in HPV-16/18 antibody avidity and HPV-specific memory B-cell response in mid-adult aged men post-dose three of the quadrivalent HPV vaccine

Strong quantitative and functional antibody responses to the quadrivalent human papillomavirus (HPV) vaccine were reported in mid-adult aged men, but there are limited data on the avidity of the antibody response and the memory B-cell response following vaccination. Although circulating antibodies induced by vaccination are believed to be the main mediators of protection against infection, evaluation of avidity of antibodies and memory B cell responses are critical for a better understanding of the vaccine immunogenicity mechanisms. Both the modified enzyme-linked immunosorbent assay (ELISA) and the enzyme-linked immunosorbent spot (ELISpot) assay are tools to measure the humoral and cellular immune responses post vaccination to characterize vaccine immunogenicity. The avidity of HPV-16 and HPV-18 specific IgG in the serum of mid-adult aged men (N = 126) who received three quadrivalent HPV vaccine doses was examined using a modified ELISA. HPV-16 memory B-cell responses were assessed via ELISpot at month 0 (prior to vaccination) and 1-month post-dose three of the vaccine (month 7). The quadrivalent vaccine induced an increase in HPV-16 and HPV-18 antibody avidity at month 7. HPV-18 avidity levels moderately correlated with anti-HPV-18 antibody titers, but no association was observed for HPV-16 antibody titers and avidity levels. The HPV-16-specific memory B-cell response was induced following three vaccine doses, however, no association with anti-HPV-16 antibody avidity was observed. Three doses of quadrivalent HPV vaccine increased antibody affinity maturation for HPV-16/18 and increased the frequency of anti-HPV-16 memory B-cells in mid-adult aged men.     

A pilot randomized study to assess immunogenicity,reactogenicity, safety and tolerability of two human papillomavirus vaccines administered intramuscularly and intradermally to females aged 18–26 years

Intradermal administration of human papillomavirus (HPV) vaccines could be dose-sparing and cost-saving. This pilot randomized study assessed Cervarix^® and Gardasil^® administered either intramuscularly or intradermally, in different doses (full-dose or reduced to 20%) by different methods (needle and syringe or PharmaJet needle-free jet injection device). Following an initial reactogenicity study of 10 male subjects, sexually naïve women aged 18–26 years were randomized to the eight study groups to receive vaccine at 0, 2 and 6 months. 42 female subjects were enrolled and complete data were available for 40 subjects. Intradermal administration of either vaccine raised no safety concerns but was more reactogenic than intramuscular administration, although still tolerable. All subjects demonstrated a seroconversion (titre ≥ 1:320) by Day 95. Further evaluation of intradermal HPV vaccination and its potential for cost reduction in resource poor settings is warranted.     

Immunogenicity and safety of a combined DTaP-IPV vaccine compared with separate DTaP and IPV vaccines when administered as pre-school booster doses with a second dose of MMR vaccine to healthy children aged 4-6 years

Combination vaccines represent one solution to the problem of increased numbers of injections during single clinic visits. A combined DTaP-IPV (Infanrix-IPV) vaccine has been developed for use as a pre-school booster. Four hundred healthy children aged 4-6 years previously primed with 4 doses of DTaP vaccine (Infanrix), 3 doses of poliovirus vaccine and 1 dose of MMR vaccine were randomized to receive single doses of either the combined DTaP-IPV vaccine or separate DTaP and IPV vaccines in a Phase II trial (DTaP-IPV-047). All children also received a second dose of MMR vaccine. Immunogenicity was assessed in serum samples taken before and 1 month after booster administration. Safety was actively assessed for 42 days post-vaccination. Non-inferiority of the DTaP-IPV vaccine to separate DTaP and IPV vaccines was demonstrated for all DTaP antigen booster response rates and poliovirus geometric mean titers of antibody ratios. Post-vaccination, > or =99.4% of children in both groups had seroprotective levels of anti-diphtheria and anti-tetanus antibodies (> or =0.1IU/mL) and seroprotective anti-poliovirus antibody titers (> or =1:8). All children in both groups were seropositive for measles, mumps and rubella antibodies, with similar post-vaccination geometric mean concentrations/titers. No significant differences were observed in the incidence of solicited local or general symptoms, unsolicited symptoms and serious adverse events between the two groups. This combined DTaP-IPV appeared safe and immunogenic when given as a booster dose at 4-6 years of age. The DTaP-IPV vaccine had no negative effect on the response to co-administered MMR vaccine, making it well-suited for use as a pre-school booster.     

Evaluation of the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine (Prevenar) administered in previously unvaccinated Spanish children aged 24 to 36 months

This study evaluates the safety and immunogenicity of pneumococcal seven-valent conjugate vaccine (Prevenar) in 115 children, aged 2-3 years (24-36 months), who have not been previously vaccinated with Prevenar. RESULTS: Safety: As for local reactions, 40% of children reported erythema, 32.2% induration and 39.1% tenderness at the injection site. Regarding systemic reactions, fever > or 38 C was recorded in 7% of patients. Other commonly reported events were decreased appetite (24.3%), restlessness (20%), and fussiness (18.3%). IMMUNOGENICITY: After vaccination, more than 98% of the subjects achieved antibody levels of > or = 0.15 microg/mL for all seven serotypes and more than 95% achieved antibody levels > or = 0.50 microg/mL for all serotypes. CONCLUSIONS: Pneumococcal seven-valent conjugate vaccine (Prevenar) was safe, well tolerated and highly immunogenic when administered in previously unvaccinated children aged 14-36 months.     

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.