Randomized placebo controlled human volunteer trial of a live oral cholera vaccine VA1.3 for safety and immune response

A live oral cholera vaccine developed from a non-toxigenic Vibrio cholerae O1 El Tor strain VA1.3 was tested in a double-blind randomized placebo controlled study for safety and immunogenicity in 304 men aged between 16 and 50 years from Kolkata, India. A dose of 5 × 10⁹ CFU (n = 186) or a placebo (n = 116) containing the diluent buffer was administered. The vaccine did not elicit adverse events except in two vaccine recipients with mild diarrhoea and vomiting. None excreted the vaccine strain. Vibriocidal antibody response developed in 105/186 (57%) and 5/116 (4%) in vaccine and placebo recipients, respectively. In a subgroup, anti-CT antibody rose (≥2-folds) in 23/30 (77%) and 6/19 (32%) in vaccine and placebo recipients, respectively. These studies demonstrate that VA1.3 at a dose of 5 × 10⁹ is safe and immunogenic in adults from a cholera endemic region.     

Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6–35 months

We report on the evaluation of the immunogenicity and reactogenicity/safety of AS03-adjuvanted vaccine against pandemic influenza A/H1N1/2009 in young children. In this open-label, randomized study, 157 healthy children aged 6–35 months received two doses (21 days apart) of split-virion inactivated A/California/7/2009 H1N1 vaccine containing either (i) 1.9 μg hemagglutinin (HA) and AS03_B (5.93 mg tocopherol) (N = 104) or (ii) 3.75 μg HA and AS03_A (11.86 mg tocopherol) (N = 53). At 21 days following the first dose of AS03_B-adjuvanted vaccine (1.9 μg HA) the percentage of children with hemagglutination-inhibition titers of ≥40 against the vaccine strain rose from 3.0% before vaccination to 100%. The seroconversion rate was 99% and the geometric mean titer (GMT) increased from 6 to 313. After the second dose the GMT increased further to 2008. The higher dose AS03_A-adjuvanted 3.75 μg HA vaccine did not further increase the immune response. Solicited symptoms reported within 7 days following vaccination were mainly mild to moderate. After the first dose of AS03_B-adjuvanted vaccine (1.9 μg HA) the most common solicited symptoms were pain at the injection site (35.6%) and irritability (31.7%). Fever (axillary ≥37.5 °C) was reported with an incidence of 20.2%. After the second dose reactogenicity tended to increase (injection site pain: 41.3%; irritability: 46.2%; fever ≥37.5 °C: 67.3%). Spontaneously reported adverse events with an intensity that prevented normal activities were documented for 2.9–6.7% of doses with only one event (vomiting) considered related to vaccination. There was one serious adverse event reported in the AS03_A-adjuvanted 3.75 μg HA vaccine group (traumatic brain injury) which was not considered as related to vaccination. In conclusion, these data suggest that a first dose of AS03_B-adjuvanted A/H1N1/2009 vaccine containing 1.9 μg HA in children 6–35 months old is highly immunogenic and that the overall reactogenicity profile is acceptable although reactions including fever tend to increase after a second dose.     

Factors associated with effectiveness of the first dose of hepatitis B vaccine in China: 1992–2005

Background

In China, the prevalence of chronic hepatitis B infection was high because of perinatal and early childhood transmission. A three-dose hepatitis B vaccine schedule with a first dose as soon as possible after birth was introduced in 1992 and generalized in 2002 in the Expanded Programme of Immunization (EPI). In 2006, a serological survey evaluated the effectiveness of vaccination.

Methods

We conducted a restricted analysis of the national serological survey that sampled children and collected information on demographic characteristics, birth history, hepatitis B vaccination and hepatitis B surface antigen (HBsAg) status as determined by ELISA testing. We compared children who received the first dose in a timely way (i.e., within 24 h of birth) with others in terms of HBsAg status, stratified by birth cohort and place of birth.

Results

Three-dose hepatitis B vaccine coverage increased from 60.8% for children born in 1992–1997 to 93.2% for children born in 2002–2005. Meanwhile, timely birth dose coverage increased from 38.7% to 74.4%. Among 29,410 children born in 1992–2005 who had received three vaccine doses and no hepatitis B immune globulin, factors associated with being HBsAg-negative in multivariate analysis included receiving a timely birth dose (p = 0.04), birth after 1998 (p < 0.001), living in an urban setting (p = 0.008) and hospital birth (p = 0.001). The relative prevalence of HBsAg among children receiving the timely birth dose was lower for children born in county or larger hospitals (0.39), intermediate in township hospitals (0.73) and highest at home (0.87).

Conclusions

Hospital birth and receiving a timely birth dose are the main determinants of the field effectiveness of the first dose of hepatitis B vaccine. Efforts to increase the proportion of hospital deliveries are key to increasing timely birth dose coverage and its effectiveness.     

Human leukocyte antigen associations with humoral and cellular immunity following a second dose of measles-containing vaccine: persistence, dampening, and extinction of associations found after a first dose

Previously we found human leukocyte antigen (HLA) associations with humoral immunity following a single dose of measles-containing vaccine. In this study, we sought to determine if HLA associations exist with humoral and cellular immunity following a second dose of measles-containing vaccine and if the associations we found with humoral immunity after the first dose persist following a second dose.We recruited a population-based sample of 346 schoolchildren, all who previously received two doses of a measles-containing vaccine. Molecular HLA classes I and II typing as well as humoral and cellular immune assays (measles-specific IgG antibody levels and lymphoproliferative response) were performed in these subjects.We found significant associations with class I HLA-B (p = 0.05) as well as class II HLA-DPB1 (p = 0.01) and -DPA1 (p = 0.03) genes for measles vaccine-induced antibody levels after the second dose. Similarly, we found significant associations with class II HLA-DQB1 (p = 0.05) and -DRB1 (p = 0.01) genes for measles-specific lymphoproliferation after the second dose.While we found HLA associations after the second dose that we previously found after the first dose of measles containing vaccine, fewer alleles had statistically significant associations, suggesting that the second dose had a dampening or extinguishing effect on the HLA associations. It appears that the second dose overcomes HLA restriction through an as yet unknown mechanism. Future studies of HLA associations should consider both the effect of dose and the role that subsequent doses might play on genetic associations found with the response to a first dose.     

Measles in Papua New Guinea: An age-specific serological survey

We aimed to determine the proportion of the population in Madang (Papua New Guinea) immune to measles infection by age groups, with respect to immunization status and study location, using dried blood sampling technology. We performed a prospective cross-sectional sero-survey. Population immunity against measles was sub-optimal (77%) and reported measles vaccine coverage in children <10 years of age was low (41%). The urban population was more susceptible to measles infection, compared with the rural population (66% vs 79% immune, aOR = 0.6, p = 0.05). Sero-conversion and long term protection rates appeared to be higher when at least one dose of vaccine was provided at or after 12 months of age (84% vs 59%, aOR = 4.3, p = 0.004). Such a dose is, however, not currently prescribed by the national immunization schedule.     

Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults

Background

Pneumococcal vaccines based on conserved protein antigens have the potential to offer expanded protection against Streptococcus pneumoniae.

Objective

To explore safety and immunogenicity of a recombinant protein vaccine candidate against S. pneumoniae composed of adjuvanted pneumococcal histidine triad protein D (PhtD).

Methods

This phase I, exploratory, open-label, single-center clinical study enrolled adults (18–50 years). Participants in a pilot safety cohort received a single intramuscular injection of 6 μg. Following safety review, 3 dose cohorts were enrolled (6, 25, and 100 μg); participants received 2 injections administered approximately 30 days apart. Assignment of the second injection and successive dose cohorts were made after blinded safety reviews after each injection at each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events, serious adverse events, and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD antibodies as measured by ELISA.

Results

Sixty-three participants were enrolled and received the pilot safety dose (n = 3) or at least 1 dose of PhtD vaccine candidate at 6 μg (n = 20), 25 μg (n = 20), or 100 μg (n = 20). No safety concerns were identified. No vaccine-related serious adverse event was reported. The most common solicited injection site reaction was pain and most common solicited systemic reactions were myalgia and headache; most reactions were mild and transient. Observed geometric mean concentrations (95% CI) were 200.99 ELISA units (148.46, 272.10), 352.07 (193.49, 640.63), and 699.15 (405.49, 1205.48) post-injection 1 in the 6, 25, and 100 μg dose cohorts, respectively, and 378.25 (275.56, 519.21), 837.32 (539.29, 1300.04), and 1568.62 (1082.92, 2272.16) post-injection 2.

Conclusions

All dose levels were safe and immunogenic. The frequency of solicited reactions was highest at the 100 μg dose. Administration of a second injection significantly increased the levels of anti-PhtD antibodies (ClinicalTrials.gov registry no. NCT01444001).     

Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine

A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N = 110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.     

Randomized,double-blind,placebo-controlled trial to evaluate the safety and immunogenicity of live oral cholera vaccine 638 in Cuban adults

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety, reactogenicity and the immunogenicity of a 2 × 10⁹ CFU dose of the 638 lyophilized live attenuated cholera vaccine for oral administration, formulated and produced at Finlay Institute, City of Havana, Cuba. Thirty-six healthy female and male adult volunteers from 18 to 40 years old were involved, clinically examined and laboratory tested after the informed consent signature. Adverse events were monitored and seroconversion rates and geometrical mean titer (GMT) of vibriocidal antibodies were tested in volunteer's sera samples. Neither serious adverse events nor other damages to the volunteers due to vaccine or placebo feeding were reported during the clinical follow-up period of this study; none of the adverse events registered within the first 72 h after inoculation were life-threatening for volunteers. Neither severe nor moderate adverse events were reported. Sixty-one percent of subjects showed mild expected adverse events in an interval lower than 24 h up to the first 72 h, 75% of these in the vaccinated group and 18% in the placebo group. Fourteen days after inoculation the GMT of vibriocidal antibodies in the vaccine group significantly increased in comparison to the placebo group. All subjects in the vaccine group (24) seroconverted (100%). Results show that this vaccine is safe, well tolerated and immunogenic in healthy female and male volunteers.     

Effectiveness of Jeryl Lynn-containing vaccine in Spanish children

We evaluated the effectiveness of the Jeryl Lynn strain vaccine in a large outbreak of mumps in Navarre, Spain, 2006–2008. Each of the 241 cases of mumps occurring in children over 15 months of age born between 1998 and 2005 was compared with 5 controls individually matched by sex, birth date, district of residence and paediatrician. Vaccination history was obtained blindly from clinical records. Conditional logistic regression was used to obtain the matched odds ratios (ORs), and effectiveness was calculated as 1 − OR. Some 70% of cases had received one dose of measles–mumps–rubella vaccine, and 24% had received two doses. Overall vaccine effectiveness was 72% (95% CI, 39–87%). Two doses were more effective (83%; 54–94%) than a single dose (66%; 25–85%). Among vaccinated children, risk was higher in those who had received the first dose after 36 months of age (OR = 3.1; 1.2–8.4) and those who had received the second dose 3 or more years before study enrolment (OR = 10.2; 1.5–70.7). Early waning of immunity in children after the second dose may contribute to reduced vaccine effectiveness for mumps prevention.     

Reduction of travellers’ diarrhoea by WC/rBS oral cholera vaccine in young,high-risk travellers

Aims

A bidirectional cohort study investigates whether pre-travel vaccination with whole cell/recombinant B subunit inactivated, killed oral cholera vaccine reduces the incidence of diarrhoea in young adult travellers to high-risk areas.

Scope

Risk of travellers’ diarrhoea was assessed according to destination and reason for travel in high-risk travellers of a travel clinic in Barcelona, Spain.Those at high-risk between January and December 2005 were advised on water/food safety and hygiene. High-risk travellers between January and December 2006 were additionally vaccinated with WC/rBS oral cholera vaccine. Data regarding diarrhoea were gathered by structured telephone interview or e-mailed questionnaire following the travellers’ return.The incidence of diarrhoea in the group vaccinated with WC/rBS oral cholera vaccine (n = 321) was 17.4%, compared with 39.7% in the non-vaccinated group (n = 337) (adjusted risk ratio 0.40). The first episode was significantly shorter in the vaccinated group (mean 2.3 days) than in the non-vaccinated group (mean 3.8 days) (p < 0.001).Conclusions: The protective effect of the WC/rBS oral cholera vaccine was 57% in the young, high-risk travellers. Vaccination with the WC/rBS oral cholera vaccine as well as food safety and hygiene advice could offer effective means of reducing the risk of diarrhoea while abroad.     

School-based vaccination of young US males: Impact of health beliefs on intent and first dose acceptance

Little is known about adolescent males and their parents with respect to intent and first dose uptake of the human papillomavirus (HPV) vaccine outside of primay care settings. The purpose of this study was to evaluate potential predictors of parental intent to vaccinate (study was conducted in November 2010–December 2012) and of first dose uptake of HPV vaccine among a sample of young adolescent males, 11–15 years of age, who received care at a school-based health center (SBHC). We also examined intent as a potential mediator of the relationships between predictors (health beliefs and perceived spousal agreement) and vaccination. Slightly more than half (n = 135 of 249) of parents reported an intention to vaccinate and 28% (n = 69) of males received their first dose of the HPV vaccine. Two of three health beliefs were significantly associated with both intention and uptake as was perceived spousal agreement. We found intention to vaccinate was a partial mediatator between the perceived benefits of HPV vaccine and first dose acceptance. We also determined that intent was a strong mediator between both general immunization benefits and perceived spousal agreement and first dose uptake. While vaccine uptake was lower than expected, particularly considering that many barriers to vaccine initiation were eliminated because of the SBHC setting, this rate is higher than in traditional settings. After controlling for intent, only perceived benefits of the HPV vaccine remained a significant predictor of first dose acceptance.     

Immunogenicity and safety of measles-mumps-rubella-varicella (MMRV) vaccine followed by one dose of varicella vaccine in children aged 15 months–2 years or 2–6 years primed with measles-mumps-rubella (MMR) vaccine

In this open, randomized, comparative study (105908/NCT00353288), 458 age-stratified children (15 months–2 years and 2–6 years) previously primed with MMR received one dose of either a combined MMRV vaccine (Priorix-Tetra™, MMRV group) or concomitant MMR and varicella vaccines (Priorix™ and Varilrix™, MMR + V group), followed 42–56 days later by another dose of varicella vaccine (Varilrix™) in both groups. Post-vaccination measles, mumps and rubella seropositivity rates and antibody geometric mean titers (GMTs) were high (99.5% for anti-measles and 100% for anti-mumps and anti-rubella) in both vaccine groups. In the two age strata, varicella seroconversion rates were, post-dose 1: ≥97.6% (MMRV), ≥96.6% (MMR + V) and, post-dose 2: 100% in both groups. Post-dose 2, anti-varicella GMTs increased respectively 14.1- and 12.6-fold (MMRV), and 9.8- and 13.1-fold (MMR + V). Both vaccine regimens were well-tolerated. Post-dose 1, the incidence of any solicited local symptom during the 4-days follow-up was ≤28.2% (MMRV) and ≤19.8% (MMR + V) and the incidence of fever >39.5 °C (rectal temperature) within 15 days was ≤2.8% (MMRV) and ≤2.6% (MMR + V). This MMRV vaccine appears an immunogenic and safe substitute for a second dose of MMR vaccine in young children. The increase in anti-varicella antibodies observed after a second dose of varicella vaccine supports a two-dose schedule for varicella-containing vaccine.     

Association of the use of MMRV in infants by pediatric infectious disease specialists with that of other affiliated providers

Background

In an effort to maximize vaccine acceptance by minimizing adverse events following immunization associated with fever, including seizures, the Advisory Committee on Immunization Practices (ACIP) recommended in 2009 the use of measles, mumps and rubella vaccine (MMR) and varicella vaccines (V) given separately (MMR + V) rather than combination MMRV as the first dose of MMR-containing vaccine to infants. We evaluated factors associated with continued administration of MMRV as the first dose in many infants despite the ACIP recommendation.

Methods

Children 12 to 23 months of age who received MMRV or MMR + V between May 1, 2010 and April 30, 2011 were identified. Patient, provider and facility characteristics associated with MMRV or MMR + V administration were analyzed by bivariate and by multilevel multivariable logistic regression analysis.

Results

Altogether, 30,017 children received the first dose of MMRV or MMR + V at 12 to 23 months of age between May 1, 2010 and April 30, 2011. Of these, 10.2% received MMRV while 89.8% received MMR + V. MMRV was more likely to be administered to children who were non-compliant with vaccine recommendations at age one (adjusted odds ratio = 1.48, 95%CI = 1.28, 1.71). In addition, administration of MMRV by a Pediatric Infectious Disease specialist affiliated with a clinic was significantly associated with an increased likelihood of administration of MMRV by other providers at that clinic (interval odds ratio 80 = 2.18, 675.94, P(OR > 1) = 95%).

Conclusions

These data suggest that while most providers followed the ACIP recommendation to administer MMR and V separately, Pediatric Infectious Disease specialists’ vaccination practices may impact compliance with ACIP recommendations by other providers. Further study of the drivers behind the use of MMRV rather than MMR + V as the first dose of measles-containing vaccine is needed to determine if reinforcement or if clarification of ACIP recommendations is needed to elucidate when MMRV might be preferred over MMR + V.     

Unadjuvanted pandemic H1N1 influenza vaccine in HIV-1-infected adults

We evaluated the immune response to a 2009 influenza A (H1N1) unadjuvanted vaccine in HIV-infected patients and assessed the boosting effect of a second dose. HIV-infected adults were enrolled and scheduled to receive the H1N1 unadjuvanted vaccine containing 15 μg of A/California/7/2009 haemagglutinin. Anti-H1N1 antibody titers were measured at enrollment and 4-8 weeks after each vaccination by using haemagglutination inhibition (HI) and virus neutralization (NT) assays. One hundred and four patients were analyzed. Seroconversion, as measured by using HI and NT assays, was observed in 52 (50.0%) patients and 49 (47.1%) patients, respectively, after the first dose. Seroconversion rate evaluated by using NT, but not HI, antibody titers was associated with HIV RNA levels of <400 copies/ml (odds ratio, 3.21; 95% CI, 1.15-8.96). Other parameters, including CD4 cell count, were not associated with seroconversion. In a cohort that received two vaccine doses at a 4-8-week interval (n = 54), the seroconversion rate and geometric mean titer for HI antibodies were 44.4% (95% CI, 30.8-58.1%) and 30.5 (95% CI, 19.9-46.9) after the first dose, respectively, and 48.1% (95% CI, 34.4-61.9%) and 39.0 (95% CI, 26.1-58.2) after the second dose, respectively. Among HIV-infected patients, the seroconversion rate was around 50% after the first dose of unadjuvanted vaccine. A second dose of vaccine had a limited boosting effect on immunity in this patient cohort.     

Trends in early childhood vaccination coverage: Progress towards US Healthy People 2010 goals

Objectives

To evaluate trends in national vaccination coverage from 2000 to 2007 among children aged 19–35 months for at least four doses of diphtheria–tetanus–pertussis vaccine (4 + DTaP), three doses of poliovirus vaccine (3 + Polio), one dose of measles–mumps–rubella vaccine (1 + MMR), three doses of Haemophilus influenzae type b vaccine (3 + Hib), three doses of hepatitis B vaccine (3 + HepB), one dose of Varicella vaccine (1 + Var), and the standard vaccine series of these six vaccines (4:3:1:3:3:1). To predict vaccination coverage levels in 2008–2010 for those vaccines that have not yet reached the Healthy People 2010 coverage targets of 90% for individual vaccines and 80% for the vaccine series.

Methods

Data were analyzed for 167,086 children aged 19–35 months in the 2000–2007 National Immunization Survey. Vaccination coverage trends were analyzed with weighted least squares linear regression models. Nonlinear Weibull and logarithmic regression models were fitted to these past results, and extrapolation was used to predict vaccination coverage levels for 4 + DTaP, 1 + Var, and the 4:3:1:3:3:1 series from 2008 to 2010.

Results

From 2000 to 2007, observed vaccination coverage increased significantly for four of the six vaccines and the standard vaccine series, and reached the 90% target for 3 + Polio, 1 + MMR, 3 + Hib, and 3 + HepB. Increases in coverage were not significant for 1 + MMR and 3 + Hib; however, coverage for these vaccines was consistently > 90% throughout the study period. Both Weibull and logarithmic regression models predicted that coverage with 1 + Var and the 4:3:1:3:3:1 series will surpass the 2010 target by 2008, while coverage with 4 + DTaP will fall short of the target at 86% in 2010.

Conclusions

The United States is well on the way toward reaching most of the Healthy People 2010 objectives for early childhood vaccination coverage. Enhanced efforts are needed to ensure that these trends continue, and to increase coverage with 4 + DTaP.     

CD4+ T-cell responses to an oral inactivated cholera vaccine in young children in a cholera endemic country and the enhancing effect of zinc supplementation

Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral^® containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10–18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P < 0.01) and IFN-γ production (P < 0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P > 0.05). The IFN-γ production was significantly higher (P < 0.01) but the blast formation comparable (P > 0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P < 0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-γ as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.     

Safety and immunogenicity of an AS03-adjuvanted A(H1N1)pmd09 vaccine administered simultaneously or sequentially with a seasonal trivalent vaccine in adults 61 years or older: Data from two multicentre randomised trials

During the 2009–2010 Northern Hemisphere influenza season, both seasonal and pandemic influenza vaccines were expected to be administered to elderly people, which is an important target group for influenza vaccination. Two multicentre randomised clinical studies were conducted in participants aged ≥61 years to assess the immunogenicity and reactogenicity following vaccination with two doses of an AS03-adjuvanted A(H1N1)pmd09 vaccine when either sequentially administered (21 days before first dose [N = 73] or 21 days after second dose [N = 72]) or co-administered (first dose [N = 84] or second dose [N = 84]) with a licensed trivalent seasonal influenza vaccine (TIV). Overall, 313 participants from 2 centres in Sweden (ClinicalTrials.gov, NCT00968890) and 6 centres in Germany (NCT00971425) were randomised to one of the four treatment groups. The AS03-adjuvanted A(H1N1)pmd09 vaccine elicited a good immune response against A(H1N1)pmd09-like virus in all treatment groups after the first and second dose, meeting and exceeding the European licensing criteria for pandemic influenza vaccines. After one dose of the AS03-adjuvanted A(H1N1)pmd09 vaccine, haemagglutination inhibition seroconversion rates ranged from 85% (95% confidence interval: 74–93%) to 93% (85–97%), seroprotection rates from 87% (76–94%) to 96% (90–99%) and geometric mean fold rise from 15 (11–19) to 20 (16–25). The haemagglutination inhibition immune responses to the AS03-adjuvanted A(H1N1)pmd09 vaccine seemed lower when TIV was administered 3 weeks before, while immune responses to TIV seemed not affected by either vaccination schedule. Solicited symptoms were more frequently reported following administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine compared to TIV, but these were mainly mild to moderate in intensity and transient in the four treatment groups. These results suggest that sequential or co-administration of the AS03-adjuvanted A(H1N1)pmd09 vaccine and TIV induced a good immune response to both vaccines and had a clinically acceptable safety profile in people aged ≥61 years.     

Oral cholera vaccination strategy: Self-administration of the second dose in urban Dhaka,Bangladesh

Cholera remains a major public health problem in many developing countries including Bangladesh. The oral cholera vaccine (OCV) is now considered a key component of the public health response to cholera. Although maintaining cold chain and organizing human resource are the major challenges of vaccine delivery to the community. Here we applied an innovative approach to second dose OCV delivery to minimize financial and logistic burdens. The purpose of this study was to assess the feasibility and compliance of second dose self-administration when the second dose was provided in a plastic bag to first dose vaccine recipients as OCV is stable for up to 42?days at ambient temperatures. We aimed to deploy vaccines (N?=?112,000) left over from other studies to 56,000 people aged?≥?one year living in Mirpur, Dhaka to see the feasibility of self-administration strategy. During vaccination, the first OCV dose (OCV1) was given from fixed sites and the second dose (OCV2) was provided in a plastic zip-lock bag for the participant to take the vaccine two weeks later at home. Participants were instructed to keep the vaccine away from light and in a dry cool place. Empty vials were collected following the end date of the scheduled second vaccination. Of the targeted population, 41,694 (74%) received the first OCV dose whereas an estimated 38,852 (93% of those receiving the first dose) received the second dose which represents a 7% drop out rate from OCV1 to OCV2. However the average two dose coverage was 69%. A survey of a subsample 2990 (from 8551) randomly selected households revealed that almost all respondents (98.75%) appreciated this new self-administration strategy and considered the strategy to be more practical and convenient than the usual method. This simplified, self-administered delivery strategy provides an ideal alternative for second-dose OCV delivery in hard-to-reach populations and resource-poor settings.