Heterologous prime-boost regimen adenovector 35-circumsporozoite protein vaccine/recombinant Bacillus Calmette-Guérin expressing the Plasmodium falciparum circumsporozoite induces enhanced long-term memory immunity in BALB/c mice

Background

Sustained antibody levels are a hallmark of immunity against many pathogens, and induction of long-term durable antibody titers is an essential feature of effective vaccines. Heterologous prime-boost approaches with vectors are optimal strategies to improve a broad and prolonged immunogenicity of malaria vaccines.

Results

In this study, we demonstrate that the heterologous prime-boost regimen Ad35-CS/BCG-CS induces stronger immune responses by enhancing type 1 cellular producing-cells with high levels of CSp-specific IFN-γ and cytophilic IgG2a antibodies as compared to a homologous BCG-CS and a heterologous BCG-CS/CSp prime-boost regimen. Moreover, the heterologous prime-boost regimen elicits the highest level of LLPC-mediated immune responses.

Conclusion

The increased IFN-γ-producing cell responses induced by the combination of Ad35-CS/BCG-CS and sustained type 1 antibody profile together with high levels of LLPCs may be essential for the development of long-term protective immunity against liver-stage parasites.     

A cell culture-derived whole-virus H5N1 vaccine induces long-lasting cross-clade protective immunity in mice which is augmented by a homologous or heterologous booster vaccination

Background

Preparation for an H5N1 influenza pandemic in humans could include priming the population in the pre-pandemic period with a vaccine produced from an existing H5N1 vaccine strain, with the possibility of boosting with a pandemic virus vaccine when it becomes available. We investigated the longevity of the immune response after one or two priming immunizations with a whole-virus H5N1 vaccine and the extent to which this can be boosted by later immunization with either a homologous or heterologous vaccine.

Methods

Mice received one or two priming immunizations with a Vero cell culture-derived, whole-virus clade 1 H5N1 vaccine formulated to contain either 750 ng or 30 ng hemagglutinin. Six months after the first priming immunization, mice received either a booster immunization with the same clade 1 vaccine or a heterologous clade 2.1 vaccine, or buffer. Humoral and cellular immune responses were evaluated before and at regular intervals after immunizations. Three weeks after booster immunization, mice were challenged with a lethal dose of wild-type H5N1 virus from clades 1, 2.1 or 2.2 and survival was monitored for 14 days.

Results

One or two priming immunizations with the 750 ng or 30 ng HA formulations, respectively, induced H5N1-neutralizing antibody titers which were maintained for ≥6 months and provided long-term cross-clade protection against wild-type virus challenge. Both humoral and cellular immune responses were substantially increased by a booster immunization after 6 months. The broadest protective immunity was provided by an immunization regimen consisting of one or two priming immunizations with a clade 1 vaccine and a boosting immunization with a clade 2.1 vaccine.

Conclusions

These data support the concept that pre-pandemic vaccination can provide robust and long-lasting H5N1 immunity which could be effectively boosted by immunization either with another pre-pandemic vaccine or with the pandemic strain vaccine.     

Comparison of immunogenicity between codon optimized HIV-1 Thailand subtype B gp140 and gp145 vaccines

HIV-1 pandemic posed an unprecedented challenge to the global health and it is believed that an effective vaccine will be the final solution against HIV-1. HIV-1 envelope is the primary immunogen in developing neutralization antibody based HIV vaccine. To define the suitable Env derived immunogen, we systemically compared the immunogenicity of gp140 and gp145 in a DNA vaccination alone and a prime-boost modalities. Two DNA vaccines and two recombinant Tiantan vaccinia vaccines (rTTV) were constructed for vaccination of female Balb/c mice. Elispot assay was used to read out the T cell immunity and ELISA assay was used to quantify antibody immunity. PLL (poly-L-leucine)-ELISA assay was used in linear antibody epitope mapping. Mice primed with gp145 tended to elicit more Env-specific T cells responses than those primed with gp140, significant difference was observed in DNA immunization alone. The ultimate T cell responses in prime-boost regimen tend to be determined mainly by the priming efficacy. Linear antibody epitope mapping displayed that sera raised by gp145 priming were vigorously reactive to more peptides than that by gp140. Our data demonstrated HIV-1 Thailand B-derived gp145 may raise higher T-cell responses and broader linear peptide-specific antibody responses than gp140 does. However, it remains to be determined that how these observations are relevant to the neutralization of antibody activities.     

Effect of needle length for response to hepatitis B vaccine in macrosomic neonates: a prospective randomized study

Objectives

The objective of this study was to determine whether use of a longer (1 in.) rather than a standard (5/8 in.) needle used for macrosomic neonates (birthweight over 4000 g) may affect antibody titers after immunization against hepatitis B virus (HBV).

Methods

Fifty nine healthy infants were vaccinated at birth, 1, and 6 months of age with hepatitis B vaccine, with follow up to 7 months of age. Infants were randomized into two groups according to needle length of first vaccine at birth. First group vaccinated with standart needle length and other group received vaccine by longer needle length.

Results

Macrosomic infants who were immunized with a longer needle achieved significantly higher antibody titers to hepatitis B surface antigen than standart needle length (median, 3890.2 vs 1311.7 mIU/mL, respectively; p = 0.001).

Conclusions

Macrosomic neonates benefit from longer needle length with higher levels of antibody titers after HBV vaccination.     

Improvement of antibody responses by HIV envelope DNA and protein co-immunization

Background

Developing HIV envelope (Env) vaccine components that elicit durable and protective antibody responses is an urgent priority, given the results from the RV144 trial. Optimization of both the immunogens and vaccination strategies will be needed to generate potent, durable antibodies. Due to the diversity of HIV, an effective Env-based vaccine will most likely require an extensive coverage of antigenic variants. A vaccine co-delivering Env immunogens as DNA and protein components could provide such coverage. Here, we examine a DNA and protein co-immunization strategy by characterizing the antibody responses and evaluating the relative contribution of each vaccine component.

Method

We co-immunized rabbits with representative subtype A or B HIV gp160 plasmid DNA plus Env gp140 trimeric glycoprotein and compared the responses to those obtained with either glycoprotein alone or glycoprotein in combination with empty vector.

Results

DNA and glycoprotein co-immunization was superior to immunization with glycoprotein alone by enhancing antibody kinetics, magnitude, avidity, and neutralizing potency. Importantly, the empty DNA vector did not contribute to these responses. Humoral responses elicited by mismatched DNA and protein components were comparable or higher than the responses produced by the matched vaccines.

Conclusion

Our data show that co-delivering DNA and protein can augment antibodies to Env. The rate and magnitude of immune responses suggest that this approach has the potential to streamline vaccine regimens by inducing higher antibody responses using fewer vaccinations, an advantage for a successful HIV vaccine design.     

Indicators of therapeutic effect in FIT-06, a Phase II trial of a DNA vaccine, GTU(®)-Multi-HIVB, in untreated HIV-1 infected subjects

Background

Combination highly active antiretroviral therapy (HAART) has significantly decreased HIV-1 related morbidity and mortality globally transforming HIV into a controllable condition. HAART has a number of limitations though, including limited access in resource constrained countries, which have driven the search for simpler, affordable HIV-1 treatment modalities. Therapeutic HIV-1 vaccines aim to provide immunological support to slow disease progression and decrease transmission. We evaluated the safety, immunogenicity and clinical effect of a novel recombinant plasmid DNA therapeutic HIV-1 vaccine, GTU^®-multi-HIVB, containing 6 different genes derived from an HIV-1 subtype B isolate.

Methods

63 untreated, healthy, HIV-1 infected, adults between 18 and 40 years were enrolled in a single-blinded, placebo-controlled Phase II trial in South Africa. Subjects were HIV-1 subtype C infected, had never received antiretrovirals, with CD4 ≥ 350 cells/mm³ and pHIV-RNA ≥ 50 copies/mL at screening. Subjects were allocated to vaccine or placebo groups in a 2:1 ratio either administered intradermally (ID) (0.5 mg/dose) or intramuscularly (IM) (1 mg/dose) at 0, 4 and 12 weeks boosted at 76 and 80 weeks with 1 mg/dose (ID) and 2 mg/dose (IM), respectively. Safety was assessed by adverse event monitoring and immunogenicity by HIV-1-specific CD4+ and CD8+ T-cells using intracellular cytokine staining (ICS), pHIV-RNA and CD4 counts.

Results

Vaccine was safe and well tolerated with no vaccine related serious adverse events. Significant declines in log pHIV-RNA (p = 0.012) and increases in CD4+ T cell counts (p = 0.066) were observed in the vaccine group compared to placebo, more pronounced after IM administration and in some HLA haplotypes (B*5703) maintained for 17 months after the final immunisation.

Conclusions

The GTU^®-multi-HIVB plasmid recombinant DNA therapeutic HIV-1 vaccine is safe, well tolerated and favourably affects pHIV-RNA and CD4 counts in untreated HIV-1infected individuals after IM administration in subjects with HLA B*57, B*8101 and B*5801haplotypes.     

Feasibility of a randomized controlled trial to evaluate Text Reminders for Immunization Compliance in Kids (TRICKs)

Objective

To pilot test the Text Reminders for Immunization Compliance in Kids (TRICKs) program to evaluate its feasibility and potential to increase immunization coverage.

Design

Randomized controlled trial (RCT).

Setting

Pediatric clinic.

Participants

Parents of newborns being discharged from a local hospital who intended to seek child health care at the University-sponsored pediatric resident and faculty clinic.

Intervention

Text message immunization reminders prior to immunization due dates.

Main Outcome Measures

Receipt and timeliness of immunizations at 2, 4 and 6 months of age.

Results

Participants (N = 90) were English (83%) or Spanish (17%) speaking. The majority were female (83%), on public insurance (59%), and had adequate health literacy (96%). Parents were married or a member of an unmarried couple (62%). Over 66% had a high school diploma or less. Greater numbers of intervention children received immunizations and were “on time” using per protocol analysis; though not statistically significance. Limitations include sample size, problematic text messaging software, and loss of phone service at 7 months for 40% of intervention parents. However, post-intervention interviews (N = 18) indicated strong support for TRICKs; 83% found the text message reminders very helpful and 17% somewhat helpful.

Discussion

Pilot testing allowed us to assess processes, including recruitment, retention, and software, which will increase the success of an RCT. Software with built-in backup systems is needed for follow-up when mobile service is interrupted. However, in spite of limitations, immunization rates were higher in the text message reminder group, though not statistically significant. Parent support and interest was high. A fully powered RCT is needed with follow-up over the full 4-3-1-3-3-1 series. Based on our results, for 80% power where we expected 90% compliance in the intervention group and 80% in the control group we need 219 per group, plus increases to address drop out and loss of follow-up.     

DNA-VLP prime-boost intra-nasal immunization induces cellular and humoral anti-HIV-1 systemic and mucosal immunity with cross-clade neutralizing activity

The immune response to HIV-1 virus-like particles (VLPs), presenting a clade A Ugandan gp120, has been evaluated in a mouse model by intra-nasal (i.n.) administration by a VLP+VLP homologous or a DNA+VLP heterologous prime-boost immunization protocol, including a HIV-1 DNA gp160/rev plasmid. Furthermore, the effect of the Eurocine lipid-based mucosal L3 adjuvant on the VLP immunogenicity has been assessed as well. The designed heterologous protocol is able to increase the env-specific humoral and cellular immune response, compared to the homologous protocol, which is to some extent increased by the administration of L3-adjuvanted VLP boosting dose. The anti-gag response is statistically increased in both homologous and heterologous protocols, particularly when the VLP boosting dose is adjuvanted. Immune sera from immunized animals exhibit >50% ex vivo neutralizing activity against heterologous A and B-clade viral isolates. An envelope B-cell epitope mapping shows an enhanced response against V3 epitopes all across the C2-V5 region in the heterologous prime-boost immunization strategy. The induction of humoral immunity at mucosal sites, which represents the main port of entry for the HIV-1 infection, is extremely relevant. In this framework, the DNA-VLP heterologous prime-boost protocol appears a promising preventive vaccine approach which can significantly benefit from specific mucosal adjuvants, as the Eurocine L3.     

Cell culture (Vero cell) derived whole-virus non-adjuvanted H5N1 influenza vaccine induces long-lasting cross-reactive memory immune response: Homologous or heterologous booster response following two dose or single dose priming

Background

Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero cell-derived whole virus non-adjuvanted H5N1 vaccine.

Methods

In one study, 281 healthy adult (18–59 years) and 280 elderly (≥60 years) subjects received two vaccinations, 21 days apart, with Vero cell-derived whole virus non-adjuvanted H5N1 vaccine (7.5 μg HA antigen A/Vietnam/1203/2004) followed by a 6, 12–15, or 24 month booster (7.5 or 3.75 μg A/Indonesia/05/2005 or A/Vietnam/1203/2004). In the other study, 230 healthy adults (18–59 years) received single dose priming (7.5 μg A/Vietnam/1203/2004) followed by a 12 month booster (7.5 or 3.75 μg A/Indonesia/05/2005). Antibody responses were assessed by microneutralization (MN) and single radial hemolysis (SRH) assay. Vaccine safety was assessed throughout.

Results

Two dose priming was equally immunogenic in adults and the elderly: >72% of subjects in each population achieved MN titers ≥1:20 after the second vaccination. Booster vaccinations at 6, 12–15, and 24 months induced substantial antibody increases to both strains: after a 7.5 μg A/Indonesia/05/2005 booster, 93–95% of adults and 72–84% of the elderly achieved MN titers ≥ 1:20 against this strain. Homologous and heterologous booster responses were higher in the 7.5 μg dose group than in the 3.75 μg dose group. Booster responses following single dose priming were similar; a 7.5 μg booster dose induced homologous MN titers ≥1:20 in 93% of subjects.

Conclusions

A Vero cell derived whole virus non-adjuvanted H5N1 influenza vaccine is well tolerated and induces long-lasting cross-clade immunological memory that can be effectively boosted 1–2 years after two dose or single dose priming, supporting its suitability for pre-pandemic vaccination.     

Impact of anti-orthopoxvirus neutralizing antibodies induced by a heterologous prime-boost HIV-1 vaccine on insert-specific immune responses

Background

The impact of anti-vector immunity on the elicitation of insert-specific immune responses is important to understand in vaccine development. HVTN 055 was a 150 person phase I randomized, controlled HIV vaccine trial of recombinant modified vaccinia Ankara (rMVA) and fowlpox (rFPV) with matched HIV-1 inserts which demonstrated increased CD8+ T-cell immune responses in the heterologous vaccine group. The controls used in this study were the empty vectors (MVA and FPV).

Methods

Anti-MVA and anti-vaccinia neutralizing antibodies (NAbs) were measured and compared with cellular and humoral HIV-1-specific immune responses.

Results

Elicitation of anti-vector responses increased with increasing dose of MVA and up to 2 administrations. Further inoculations of MVA (up to 5) did not increase the magnitude of the anti-MVA response but did delay the anti-vector NAb titre decay. There was no evidence that the insert impaired the anti-vector response, nor that anti-vector immunity attenuated the insert-specific responses.

Conclusion

Two doses of MVA may be ideal for the elicitation of orthopoxvirus immune responses with further doses maintaining increased titres against the vector. We found no evidence that eliciting HIV insert- or MVA vector-specific immune responses interfered with elicitation of immune responses to the other.     

Human papillomavirus vaccination and sexual behaviour: cross-sectional and longitudinal surveys conducted in England

Objective

To examine whether HPV vaccination influences sexual behaviour in adolescent girls, either by giving them a ‘green light’ to have sex, or because perceived protection afforded by the vaccine permits compensatory risky sexual behaviour.

Design

Cross-sectional and longitudinal surveys.

Setting

Seven English schools.

Main outcome measures

Self-reported sexual behaviour.

Participants

The cross-sectional survey included 1053 girls (mean age 17.1 years) who had (n = 433 recruited in March 2010) or had not (n = 620 recruited in March 2009) been offered the HPV vaccine. The longitudinal survey included 407 girls (mean age 17.5 years) who had been offered HPV vaccination and had either received at least one dose (n = 148) or had not received any doses (n = 259).

Results

In the cross-sectional survey, the group of girls who had been offered the HPV vaccine were no more likely to be sexually active than the group of girls who had not been offered the HPV vaccine. In the longitudinal survey, the vaccinated group were no more likely to have changed their condom use or increased their total number of sexual partners than the unvaccinated group.

Conclusions

Neither being offered the HPV vaccine nor receiving it affected sexual behaviour.     

Characterizing providers' immunization communication practices during health supervision visits with vaccine-hesitant parents: a pilot study

Objective

To determine the feasibility of using direct observation of provider–parent immunization discussions and to characterize provider communication practices with vaccine-hesitant parents.

Methods

Over a 6 month period in 2010, we videotaped immunization discussions between pediatric providers and vaccine-hesitant parents during health supervision visits involving children 2–15 months old (N = 24) in the Seattle area, Washington, USA. Videotapes were analyzed using the qualitative method of conversation analysis.

Results

We approached 96 parents seen by 9 different providers. Of those who were eligible (N = 56), we enrolled 43% (N = 24). Four videotaped visits were excluded from analysis for failure to obtain parental HIPAA authorization. Of the remaining 20 visits, there were ≥2 visits each that involved children aged 2, 4, 6, 9, 12, and 15 months, and all videotaped visits contained at least a brief immunization discussion. We identified 6 communication practices and several behavior types within each practice relevant to immunization: Practice 1, providers’ initiations of the topic of vaccination; Types: participatory or presumptive format; Practice 2, parents’ responses to providers’ topic initiations; Types: strong or weak acceptance or resistance; Practice 3, providers’ follow-ups to parent's responses; Types: no, immediate, or delayed pursuit; Practice 4, parents’ vaccine-related questions or statements; Types: fact- or concern-based; Practice 5, providers’ explicit solicitations of parent's questions/concerns; Types: designed to discourage or encourage discussion; and Practice 6, parents’ responses to providers’ solicitations of questions/concerns; Types: no question or fact- or concern-based inquiry.

Conclusion

Direct observation of immunization discussions in the primary care pediatric setting is feasible and yields insight into several provider–parent immunization communication practices that are worthy of further study to determine which are effective at improving parental acceptance of immunization.     

Antibody persistence in mothers one year after pneumococcal immunization in pregnancy

Background

Pneumococcal infections are a significant cause of morbidity and mortality, and young infants are particularly vulnerable to infection. Maternal immunization can protect infants, but there are limited data on the duration of pneumococcal vaccine antibody in pregnant women. We report on maternal antibody concentrations one year after immunization with 23-valent pneumococcal polysaccharide (23vPPS) vaccine.

Method

The Mother's Gift study randomly assigned 340 pregnant Bangladeshi mothers between ages 18 and 36 to receive either inactivated influenza vaccine (Fluarix^®) or the 23vPPS vaccine (Pneumovax^®) during the third trimester. Sera were collected before immunization, at delivery, and at one year post-delivery. We determined anti-capsular IgG antibody to 9 pneumococcal serotypes by a multiplex Luminex ELISA. We report antibody geometric mean concentrations (GMCs) for 9 serotypes, 12 month/delivery geometric mean ratios (GMRs) and proportions seroprotected (>0.35 mcg/mL) in 23vPPS vaccine recipients and controls at delivery and at 12 months.

Results

Among pneumococcal vaccinees, GMCs remained stable, with an overall 12 month/delivery GMR of 0.83 (95% CI, 0.75–0.92). In the control group, GMCs increased with a mean ratio of 1.98 (95% CI, 1.81–2.17; P < 0.0001). GMCs in these vaccinees did not decline significantly in the 12 months after antenatal immunization.

Conclusion

GMCs in these adult vaccinees and controls did not decline significantly in the 12 months after antenatal immunization. Interestingly, mothers who did not receive 23vPPS in pregnancy show a substantial increase of GMC for most serotypes in the first year after immunization. Further studies are needed to determine the need for repeat doses of 23vPPS vaccine in subsequent pregnancies more than a year later.     

Efficacy of ceftriaxone and doxycycline in the treatment of early syphilis

Introduction

An increase of syphilis cases has been recorded in the past few decades, especially among HIV-infected patients. These patients often present with concomitant primary and secondary lesions or extensive presentations of syphilis.

Objective

Our goal was to compare alternative regimens to the recommended penicillin treatment.

Method

We retrospectively studied 116 patient files (80% HIV1-infected) treated for a first episode of early syphilis.

Results

Patients mainly presented with symptoms of secondary syphilis. In 15.5% of the cases patients were asymptomatic and 17.2% of patients with secondary syphilis presented with neurologic or ophthalmic symptoms. Some less usual clinical presentations included diffuse polyadenopathy or isolated fever. The time to serological response was similar among those treated with benzathine-penicillin (n = 52), ceftriaxone (n = 49), or doxycycline (n = 15).

Conclusion

Ceftriaxone and doxycycline could be suitable alternatives to penicillin in the treatment of early syphilis in HIV-infected patients. These two treatments have a concomitant effectiveness even for asymptomatic forms of neurosyphilis.     

Hepatitis B vaccination coverage and uptake in prisons across England and Wales 2003-2010: a retrospective ecological study

Objective

To describe the custodial hepatitis B vaccination programme performance and examine these data by geographical region and prison category.

Design

Retrospective ecological study.

Data source

Health Protection Agency (HPA) published data.

Setting

Custodial primary healthcare providers located in prisons across England and Wales.

Participants

147 prisons which reported vaccination data between July 2003 and April 2010 to the HPA Prison Infection Prevention team.

Main outcome measures

Hepatitis B vaccination coverage (July 2003 to April 2010) and uptake (December 2007 to April 2010).

Results

Median hepatitis B vaccination coverage was 22% (interquartile range [IQR] 5–49%) and uptake was 36% (IQR 16–59%). Vaccination coverage varied significantly between July 2003 and November 2007 compared to December 2007 and April 2010 (median 12% [IQR 2–31%] versus median 48% [IQR 26–67%], Mann–Whitney W = 14,689,158.0, p < 0.001). There was significant variation between vaccination coverage (Kruskal–Wallis H = 613.44, DF = 9, p < 0.001) and uptake (Kruskal–Wallis H = 247.99, DF = 9, p < 0.001) across the HPA regions. Compared to England and Wales, estimated population median vaccination coverage was significantly (p ≤ 0.05) lower in three regions and one prison category and higher in four regions and seven prison categories; estimated population median vaccination uptake was significantly lower in three regions and three prison categories and higher in two regions and four prison categories.

Conclusion

Prisoners are a vulnerable group with a high prevalence of hepatitis B infection and the custodial setting plays an important role in the delivery of hepatitis B vaccination to this hard to reach group. This study suggests that variation in hepatitis B vaccination coverage and uptake may exist by geographical region and prison category. Further research is required to confirm and identify possible explanations for our findings.     

Pediatric influenza immunization in an integrated safety net health care system

Objective

In 2008 the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) recommended that all children aged 6 months to 18 years receive annual influenza vaccine. Full pediatric influenza administration has proven difficult. We compared rates of full influenza immunization between a safety net health care system and CDC sentinel sites and evaluated sociodemographic factors associated with full influenza immunization.

Patients and methods

We matched influenza immunization data for 2008–2009 from a health care system immunization registry with patient demographic/billing data and compared rates to CDC sentinel sites using bivariate analysis. We evaluted immunization rates by patient characteristics using multivariate analysis.

Results

Full influenza immunization was achieved in 32% of Denver Health (DH) children compared to 12% at the CDC sites (p < 0.001). The largest differences occurred in children aged 11–12 and 13–18 years, 47% DH vs 12% CDC sites, and 33% DH vs 9% CDC sites respectively, (p < 0.001 for both). In multivariate analysis, DH children were more likely to be immunized if they were Asian, Odds Ratio (OR) 1.59 95%CI (CI) 1.32–1.91, or Hispanic OR 1.18 CI 1.07–1.30, compared to white, spoke Spanish OR 1.19 CI 1.13–1.26, or other non-English language OR 2.05 CI 1.80–2.34, and had a greater number of visits for well care OR 2.86 CI 2.74–2.98 and sick/follow-up care OR 1.59 CI 1.56–1.62, during the influenza season. They were less likely to be immunized if they had commercial insurance OR 0.68 CI 0.62–0.75 or were uninsured OR 0.77 CI 0.72–0.80, compared to Medicaid/SCHIP.

Conclusions

Using immunization registry prompts, standing orders, multiple sites and visit types for immunization, an integrated safety net health care system had higher full influenza immunization rates than the CDC sentinel sites singularly or collectively. These procedures can be applied elsewhere to improve influenza immunization rates.     

Factors mediating seasonal and influenza A (H1N1) vaccine acceptance among ethnically diverse populations in the urban south

Objective

We examined the acceptability of the influenza A (H1N1) and seasonal vaccinations immediately following government manufacture approval to gauge potential product uptake in minority communities. We studied correlates of vaccine acceptance including attitudes, beliefs, perceptions, and influenza immunization experiences, and sought to identify communication approaches to increase influenza vaccine coverage in community settings.

Methods

Adults ≥18 years participated in a cross-sectional survey from September through December 2009. Venue-based sampling was used to recruit participants of racial and ethnic minorities.

Results

The sample (N = 503) included mostly lower income (81.9%, n = 412) participants and African Americans (79.3%, n = 399). Respondents expressed greater acceptability of the H1N1 vaccination compared to seasonal flu immunization (t = 2.86, p = 0.005) although H1N1 vaccine acceptability was moderately low (38%, n = 191). Factors associated with acceptance of the H1N1 vaccine included positive attitudes about immunizations [OR = 0.23, CI (0.16, 0.33)], community perceptions of H1N1 [OR = 2.15, CI (1.57, 2.95)], and having had a flu shot in the past 5 years [OR = 2.50, CI (1.52, 4.10). The factors associated with acceptance of the seasonal flu vaccine included positive attitudes about immunization [OR = 0.43, CI (0.32, 0.59)], community perceptions of H1N1 [OR = 1.53, CI (1.16, 2.01)], and having had the flu shot in the past 5 years [OR = 3.53, CI (2.16, 5.78)]. Participants were most likely to be influenced to take a flu shot by physicians [OR = 1.94, CI (1.31, 2.86)]. Persons who obtained influenza vaccinations indicated that Facebook (χ² = 11.7, p = 0.02) and Twitter (χ² = 18.1, p = 0.001) could be useful vaccine communication channels and that churches (χ² = 21.5, p < 0.001) and grocery stores (χ² = 21.5, p < 0.001) would be effective “flu shot stops” in their communities.

Conclusions

In this population, positive vaccine attitudes and community perceptions, along with previous flu vaccination, were associated with H1N1 and seasonal influenza vaccine acceptance. Increased immunization coverage in this community may be achieved through physician communication to dispel vaccine conspiracy beliefs and discussion about vaccine protection via social media and in other community venues.     

PedVacc 002: A phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi

Background

A safe, effective vaccine for breastfeeding infants born to HIV-1-positive mothers could complement antiretroviral therapy (ART) for prevention of mother-to-child transmission of HIV-1. To date, only a few HIV-1 vaccine candidates have been tested in infants.

Trial design

A phase I/II randomized controlled trial PedVacc 002 was conducted to determine the safety and immunogenicity of a single, low dose of MVA.HIVA vaccine delivered intramuscularly to healthy 20-week-old infants born to HIV-1-positive mothers in Nairobi, Kenya.

Methods

Pregnant HIV-1-positive women in the 2nd/3rd trimester of gestation were enrolled, provided with ART and self-selected their infant-feeding modality. Infants received nevirapine and cotrimoxazole prophylaxis. At 20 weeks of age, eligible HIV-1-negative infants were randomized to vaccine versus no-treatment arms and followed to 48 weeks of age for assessments of vaccine safety, HIV-1-specific T-cell responses and antibodies to routine childhood vaccines.

Results

Between February and November 2010, 182 mothers were screened, 104 were eligible and followed on ART during pregnancy/postpartum, of whom 73 had eligible infants at 20 weeks postpartum. Thirty-six infants were randomized to vaccine and 37 to no treatment. Eighty-four percent of infants breastfed, and retention at 48 weeks was 99%. Adverse events were rare and similar between the two arms. HIV-1-specific T-cell frequencies in interferon-γ ELISPOT assay were transiently higher in the MVA.HIVA arm (p = 0.002), but not above the threshold for a positive assay. Protective antibody levels were adequate and similar between arms for all routine childhood vaccines except HBV, where 71% of MVA.HIVA subjects compared to 92% of control subjects were protected (p = 0.05).

Conclusions

This trial tested for the first time an MVA-vectored candidate HIV-1 vaccine in HIV-1-exposed infants in Africa, demonstrating trial feasibility and vaccine safety, low immunogenicity, and compatibility with routine childhood vaccinations. These results are reassuring for use of the MVA vector in more potent prime-boost regimens.     

Risk factors for low vaccination coverage among Roma children in disadvantaged settlements in Belgrade, Serbia

Background

Full vaccination coverage for children under 59 months of age in Serbia is over 90%. This study assesses vaccination coverage and examines its association with birth registration among Roma children who resided in disadvantaged settlements in Belgrade, Serbia.

Methods

The First Roma Health and Nutrition Survey in Belgrade settlements, 2009, was conducted among households of 468 Roma children between the ages of 6–59 months. The 2005 WHO Immunization Coverage Cluster Survey sampling methodology was employed. Vaccinations were recorded using children's vaccination cards and through verification steps carried out in the Primary Health Care Centers. For those who had health records the information on vaccination was recorded.

Results

About 88% of children had vaccination cards. The mean rate of age appropriate full immunization was 16% for OPV and DTP and 14.3% for MMR. Multivariate analyses indicated that children whose births were registered with the civil authorities were more likely to have their vaccination cards [OR = 6.1, CI (2.5, 15.0)] and to have their full, age appropriate, series vaccinations for DTP, OPV, MMR and HepB [OR = 3.8, CI (1.5, 10.0), OR = 3.2, CI (1.5, 6.6), OR = 4.8, CI (1.1, 21.0), OR = 5.4, CI (1.4, 21.6), respectively].

Conclusions

The immunization coverage among Roma children in settlements is far below the WHO/UNICEF MDG4 target in achieving prevention and control of vaccine preventable diseases. It demonstrates the need to include “invisible” populations into the health systems in continuous, integrated, comprehensive, accessible and sensitive modes.     

Eliciting broad neutralizing antibody to HIV-1: envelopes of different lentivirus cross immunization by prime-boost vaccination

The greatest challenge of HIV vaccine development lies in the diversity of circulating HIV-1 strains. For an effective vaccine, neutralizing antibodies are assumed to be of crucial importance, but previous attempts results only very limited breadth and potency of Nab titer. While the amino acid sequences of lentivirus envelope have many differences, those envelope proteins share almost same structural conformations. If the envelopes of different lentivirus were used immune animals, the response to the conserved sites will be strengthened while the un-conserved sites will not be. In this study, compared to only protein immunization regimen, HIV-1 CN54 gp140 DNA prime and protein boost strategy generated Nab titer increased significantly. So, the prime-boost strategy and HIV-1 CN54 gp140 protein were employed to different lentivirus cross immunization schedule. The results indicated that, the different lentivirus and HIV-1 cross immune by prime-boost strategy elicited breath and potency neutralization antibody to tier 1, tier 2, and tier 3 viruses with 14 tested viruses. To tested tier 2 and tier 3 viruses, in SIV and HIV-1 cross immunization group, the neutralization breadth of ID50 is 91.7% and the breadth of ID70 is 50%; in HIV-1, FIV and SIV cross immunization group, the breadth of ID50 is 83.3% and the breadth of ID70 is 58.3%, while in only HIV-1 vaccinated group, the breadth of ID50 is 75% and the breadth of ID70 is only 25%. These data demonstrate that HIV-1 and different lentivirus especially with SIV cross immunization by prime-boost strategy elicit broad neutralizing antibodies much better than only HIV-1 immunization.