Going social: Success in online recruitment of men who have sex with men for prevention HIV vaccine research

ObjectiveTo compare the use of four different social media sites to recruit men who have sex with men (MSM) and transgender women to a phase 2b HIV prevention vaccine trial, HVTN 505.DesignRetrospective, observational study.MethodsThe University of Pennsylvania HIV Vaccine Trials Unit (Penn HVTU) employed street outreach and online recruitment methods to recruit participants for HVTN 505 using a combination of national recruitment images/messages with Philadelphia-specific language and imagery. We compared the efficiency (number of enrolled participants per number of completed phone screens) and effectiveness (number of enrolled participants per time interval employed) of each strategy, as well as the demographics and risk behaviors of the populations.ResultsOnline recruitment strategies populated 37% (71/191) of trial participants at our site. Among the four social media strategies employed, 45.1% (32/71) were enrolled through Facebook, 16.9% (12/71) through Craigslist, 15.5% (11/71) through a web-based marketing company (WBMC), and 22.5% (16/71) via GRINDR. The number of participants enrolled per month of strategy and the months the strategy was employed were Facebook - 32(33 months), Craigslist - 12(33 months), WBMC - 11(6 months), and GRINDR - 16(0.56 months). In-person and online recruitment strategies yielded participants of similar demographics and levels of risk behavior.ConclusionUse of several social media recruitment modalities produced large numbers of MSM engaging in high risk behavior and willing to participate in an HIV prevention vaccine trial. In comparison to other social media and online strategies, recruitment via GRINDR was the most effective.     

A case for preART-adjusted endpoints in HIV therapeutic vaccine trials

BackgroundIn a randomized, double-blind, placebo-controlled phase 2 clinical trial of Vacc-4x, a peptide-based therapeutic HIV-1 p24^Gag vaccine candidate, 135 HIV-infected participants (vaccine:placebo = 92:43) received a series of six immunizations while on combination antiretroviral therapy (cART). At week 28, all participants underwent an analytical treatment interruption (ATI) for up to 24 weeks. preART VL appeared to be higher among Vacc-4x recipients. Based on a previous analysis, during ATI viral load (VL) appeared to be lower in Vacc-4x recipients, but no difference in CD4 level was observed between Vacc-4x and placebo groups. We propose fold-change-based endpoints and report comparative analyses accounting for imbalanced preART VL and missing data.MethodsAll analyses included per-protocol (PP) participants who received the full immunization and underwent ATI. Linear regression models were used to identify predictors of study endpoints and to estimate the vaccine effect based on fold changes in CD4 counts or VL over preART values at week 40 or at set-point (geometric mean over weeks 48 and 52 values). We adjusted for potential baseline factors and used a multiple imputation approach to account for missing endpoints due to cART resumption or dropout. P-values were adjusted for multiple comparisons using q-values.ResultspreART VL and CD4 count were significant predictors of study endpoints. The vaccine recipients had a higher fold change in week 40 CD4 counts (vaccine vs. placebo mean fold-change difference = 0.08; p = 0.02; q = 0.03), a higher fold change in CD4 count set-point (0.06; p = 0.06; q = 0.07), a lower fold change in week 40 VL (−0.47; p = 0.03; q = 0.05), and a lower fold change in VL set-point (−0.50; p = 0.02; q = 0.03).ConclusionsThese exploratory analyses consistently suggested that Vacc-4x provided positive effects on both CD4 counts and VL. Future HIV therapeutic vaccine studies may adopt similar preART-adjusted endpoints and missing data imputation methods in vaccine effect evaluations.     

Hepatitis B vaccination uptake and correlates of serologic response among HIV-infected and uninfected men who have sex with men (MSM) in Bangkok,Thailand

BackgroundVaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM.MethodologyHBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses.Results511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p < 0.0001). Median pre-vaccination IgG was higher among non-responders than responders overall (1238.9.0 vs. 1057.0 mg/dL, p = 0.003) and among HIV-infected participants (1534.0 vs. 1244.5 mg/dL, p = 0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3 mg/dL, p = 0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV-negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1 mg/dL, respectively, p < 0.0001). Among HIV-infected participants, median CD4 count in non-responders was 378 cells/μL vs. 431 cells/μL in responders (p = 0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p = 0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p < 0.01).ConclusionsHIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure.     

Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine

BackgroundVaccine-induced mucosal immune responses may be critical for protection against HIV infection, but may also result in short or long-term changes that enhance susceptibility to infection in some individuals, such as those with baseline seroreactivity to vaccine vector antigens. We examined cellular immune responses in blood and gut mucosal tissue roughly two years following vaccination with placebo or the Step study vaccine MRKAd5/HIV-1.MethodsParticipants vaccinated with either placebo or MRKAd5/HIV-1 during participation in HVTN 071, and HVTN 502/Merck 023 underwent phlebotomy and colonic mucosal biopsies via flexible sigmoidoscopy at two timepoints roughly six months apart. After isolation of mononuclear cells, we compared cellular phenotypes and intracellular cytokine responses in vaccine and placebo recipients with and without baseline serological reactivity to Ad5.ResultsSurface expression of activation and gut-homing markers were elevated on CD4 + and CD8 + gut mucosal mononuclear cells (GMMC) in comparison with PBMC (p < 0.01), but were not significantly affected by baseline Ad5 serostatus or receipt of MRKAd5/HIV-1. ICS responses to stimulation with vaccine antigens were of low frequency and magnitude. Ad5 vector responses were seen in vaccinees and baseline seropositive individuals. CD4 + responses to vector antigens were more common in GMMC than PBMC (p < 0.01) and CD8 + responses to HIV gag insert antigens were more frequent in Ad5 seropositive than Ad5 seronegative individuals (p = 0.03).ConclusionVaccination with the Ad5 vectored candidate HIV vaccine MRKAd5/HIV-1 does not lead to long-term changes in the activation state of mucosal CD4 + or CD8 + T lymphocytes regardless of baseline Ad5 serostatus. The findings of this study do not reveal a basis for enhanced susceptibility to HIV infection two years post vaccination.     

Zika virus knowledge,attitudes, and vaccine interest among university students

BackgroundZika virus vaccine development is underway. We examined interest in receiving a Zika virus vaccine (after one becomes commercially available) among students at a large public university in Northern Virginia.MethodsAn online survey of Zika virus-related knowledge, attitudes, and interest in receiving a Zika vaccine was completed by 619 undergraduate students in April, 2016. Stepwise logistic regression with backward elimination was used to identify the variables most strongly associated with interest in being vaccinated against Zika virus.ResultsMore than half of participants (52.8%) reported that they would be likely or very likely to be vaccinated against Zika virus. Vaccination interest was significantly higher among participants who received an influenza vaccine in the past year (p = 0.002), had higher levels of knowledge about Zika virus (p = 0.046), reported knowing where to access information about Zika virus (p = 0.041), had higher perceived susceptibility to Zika virus (p < 0.001), and believed that the U.S. Government should prioritize actions to control Zika virus (p = 0.001).ConclusionsCommunication and intervention strategies encouraging vaccine uptake may benefit from increasing knowledge of Zika virus, addressing perceived susceptibility, and reaching students, travelers, and others who may be seeking information about prevention of Zika virus and other emerging infectious diseases.     

HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine

ObjectiveTo evaluate the immunogenicity and safety of the quadrivalent HPV (qHPV) vaccine in HIV-positive women over 24 months.DesignBetween November 2008 and December 2012, 372 women aged 15 and older were enrolled from 14 Canadian HIV outpatient clinics in an open label cohort study. The qHPV vaccine (0.5 mL) was administered intramuscularly at months 0, 2 and 6. The primary study endpoint was seroconversion to any of the HPV types targeted by the qHPV vaccine. Antibody levels were measured at 0, 2, 7, 12, 18, and 24 months. Adverse events were recorded throughout.ResultsOf 372 participants enrolled, 310 (83%) received at least one dose of the qHPV vaccine and 277 (74%) received all three doses. Ninety-five percent (293/308) were seronegative for at least one vaccine type at baseline. The median age was 38 years (IQR 32–45, range 15–66), 36% were white, 44% black and 13% were of Indigenous origin. Seventy-two percent of participants had a suppressed HIV viral load (VL < 40 c/ml) at baseline, with a median CD4 count of 510 cells/mm³ (376–695). Month 7 HPV type-specific seroconversion rates were 99.0%, 98.7%, 98.1% and 93.6% for HPV types 6, 11, 16 and 18 respectively in the per-protocol population. Participants with suppressed HIV VL at first vaccine had a 1.74–3.05 fold higher peak antibody response compared to those without (p from 0.006 to <0.0001).ConclusionsThis study is the first to examine the qHPV vaccine in HIV-positive women out to 24 months and the first to include HIV-positive women through to age 66. The qHPV vaccine was well tolerated, and highly immunogenic. As women with suppressed viral load had higher antibody responses, planning HPV vaccination to occur when persons are virologically suppressed would be optimal for maximizing immune response. Findings provide strong evidence that older HIV-positive women can still benefit from HPV vaccination.Clinical trial registration: http://www.isrctn.com/ISRCTN33674451     

What predicts postpartum pertussis booster vaccination? A controlled intervention trial

Background‘Cocooning’ aims to protect susceptible infants from pertussis via caregiver vaccination. Control trials evaluating educational interventions to promote cocooning are lacking. We evaluated the role of message-framing vs. standard health information in promoting pertussis vaccination.MethodsWe recruited postpartum women from a maternity hospital in Sydney, Australia (November 2010–July 2012). Participants self-completed a pertussis knowledge and attitudes questionnaire. We then assigned pertussis-susceptible (no pertussis vaccine ≤10 years) participants to receive a gain-framed, loss-framed pamphlet or control (Government Pertussis factsheet) using weekly sequential block allocation. Next, participants were offered a pertussis vaccine (dTpa) and completed a post-questionnaire on discharge.ResultsA baseline questionnaire was completed for 96.4% (1433/1486) of postpartum women approached. Missing data was excluded (n = 29). Next, participants (1404) were screened for vaccine status: 324 (23%) reported prior pertussis booster vaccine receipt, leaving 1080 participants requiring vaccination. Among susceptible mothers, 70% (754/1080) were vaccinated post-intervention. Rates were similar between ‘gain’, ‘loss’ or ‘control’ pamphlets (69.1% vs. 71.8% vs. 68.8%; p = 0.62). Intention to be vaccinated (OR 2.46, p < 0.001; 95% CI: 1.69–3.58), perceived vaccine benefits (OR: 1.61, p < 0.001; 95% CI: 1.25–2.15) and having received a vaccine recommendation (OR 1.68; p = 0.025; 95% CI: 1.07–2.65) were independent predictors of vaccine uptake. At discharge, overall pertussis vaccine coverage had increased from 23% to 77% among women screened (1078/1404).ConclusionA cocooning strategy for pertussis vaccination can be highly effective when partially implemented within maternity hospitals, with information accompanied by a funded vaccine. Mothers were highly receptive to vaccination in the postnatal ward: facts about pertussis were as effective as message-framing in promoting a high uptake of 70%. Perceived vaccine benefits, intentions and vaccine recommendation were important predictors of uptake. Our intervention trial increased the existing pertussis vaccine coverage of 23–77%.     

A study of vaccine-induced immune pressure on breakthrough infections in the Phambili phase 2b HIV-1 vaccine efficacy trial

IntroductionThe Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic.Materials and methodsA sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients. Vaccine coverage was estimated by computing the percentage of 9-mers that were exact matches to the vaccine insert.ResultsThere was significantly greater protein distances from the vaccine immunogen sequence in Gag (p = 0.045) and Nef (p = 0.021) in viruses infecting vaccine recipients compared to placebo recipients. Twenty-seven putative sites of vaccine-induced pressure were identified (p < 0.05) in Gag (n = 10), Pol (n = 7) and Nef (n = 10), although they did not remain significant after adjustment for multiple comparisons. We found the epitope sieve effect in Step was driven by HLA A102:01; an allele which was found in low frequency in Phambili participants compared to Step participants. Furthermore, the coverage of the vaccine against subtype C Phambili viruses was 31%, 46% and 14% for Gag, Pol and Nef, respectively, compared to subtype B Step virus coverage of 56%, 61% and 26%, respectively.DiscussionThis study presents evidence of sieve effects in Gag and Nef; however could not confirm effects on specific amino acid sites. We propose that this weaker signal of vaccine immune pressure detected in the Phambili study compared to the Step study may have been influenced by differences in host genetics (HLA allele frequency) and reduced impact of vaccine-induced immune responses due to mismatch between the viral subtype in the vaccine and infecting subtypes.     

Safety of Russian-backbone seasonal trivalent,live-attenuated influenza vaccine in a phase II randomized placebo-controlled clinical trial among children in urban Bangladesh

IntroductionLive-attenuated influenza vaccines (LAIVs) have the potential to be affordable, effective, and logistically feasible for immunization of children in low-resource settings.Material and methodsWe conducted a phase II, randomized, double-blind, parallel group, placebo-controlled trial on the safety of the Russian-backbone, seasonal trivalent LAIV among children aged 24 through 59 months in Dhaka, Bangladesh in 2012. After vaccination, we monitored participants for six months with weekly home visits and study clinic surveillance for solicited and unsolicited adverse events, protocol-defined wheezing illness (PDWI), and serious adverse events (SAEs), including all cause hospitalizations.ResultsThree hundred children were randomized and administered LAIV (n = 150) or placebo (n = 150). No immediate post-vaccination reactions occurred in either group. Solicited reactions were similar between vaccine and placebo groups during the first 7 days post-vaccination and throughout the entire trial. There were no statistically significant differences in participants experiencing PDWI between LAIV and placebo groups throughout the trial (n = 13 vs. n = 16, p = 0.697). Of 131 children with a history of medical treatment or hospitalization for asthma or wheezing at study entry, 65 received LAIV and 66 received placebo. Among this subset, there was no statistical difference in PDWI occurring throughout the trial between the LAIV or placebo groups (7.7% vs. 19.7%, p = 0.074). While there were no related SAEs, LAIV recipients had six unrelated SAEs and placebo recipients had none. These SAEs included three due to traumatic injury and bone fracture, and one each due to accidental overdose of paracetamol, abdominal pain, and acute gastroenteritis. None of the participants with SAEs had laboratory-confirmed influenza, wheezing illness, or other signs of acute respiratory illness at the time of their events.ConclusionsIn this randomized, controlled trial among 300 children aged 24 through 59 months in urban Bangladesh, Russian-backbone LAIV was safe and well tolerated. Further evaluation of LAIV safety and efficacy in a larger cohort is warranted.     

Brief education to promote maternal influenza vaccine uptake: A randomized controlled trial

BackgroundAlthough pregnant women are the highest priority group for seasonal influenza vaccination, maternal influenza vaccination rates remain suboptimal. The purpose of this study was to evaluate the effect of a brief education intervention on maternal influenza vaccine uptake.MethodsDuring the 2013–14 and 2014–15 influenza seasons, we recruited 321 pregnant women from the antenatal clinics of 4 out of 8 public hospitals in Hong Kong with obstetric services. Hospitals were geographically dispersed and provided services to pregnant women with variable socioeconomic backgrounds. Participants were randomized to receive either standard antenatal care or brief one-to-one education. Participants received telephone follow-up at 2 weeks postpartum. The primary study outcome was self-reported receipt of influenza vaccination during pregnancy. The secondary outcomes were the proportion of participants who initiated discussion about influenza vaccination with a health care professional and the proportion of participants who attempted to get vaccinated.ResultsCompared with participants who received standard care, the vaccination rate was higher among participants who received brief education (21.1% vs. 10%; p = 0.006). More participants in the education group initiated discussion about influenza vaccination with their HCP (19.9% vs. 13.1%; p = 0.10), but the difference was not statistically significant. Of participants who did not receive the influenza vaccine (n = 271), 45 attempted to get vaccinated. A significantly higher proportion of participants who attempted to get vaccinated were in the intervention group (82.2% vs. 17.8%; p < 0.001). If participants who had attempted vaccination had received the vaccine, vaccination rates would have been substantially higher (44.1% vs. 15%; p < 0.001). Twenty-six participants were advised against influenza vaccination by a healthcare professional, including general practitioners, obstetricians, and nurses.ConclusionAlthough brief education was effective in improving vaccination uptake among pregnant women, overall vaccination rates remain suboptimal. Multicomponent approaches, including positive vaccination recommendations by healthcare professionals, are needed to promote maternal influenza vaccination.Clinical Trial Registration: www.clinicaltrials.gov (NCT01772901).     

Association between TLR3 rs3775291 and resistance to HIV among highly exposed Caucasian intravenous drug users

BackgroundTLR3 recognizes dsRNA and triggers immune responses against RNA and DNA viruses. A polymorphism in TLR3, rs3775291 (Leu412Phe), has been associated with the increased susceptibility to enteroviral myocarditis, protection against tick-borne encephalitis virus and HIV-1 infection. We investigated Caucasian intravenous drug users (IDUs) and blood donors in order to evaluate the associations between TLR3 genotypes and susceptibility to HIV infection.Materials and methodsA total of 345 Caucasian IDUs were recruited, 50% of them were HIV positive, 89% HCV and 77% HBV positive. Based on their history of needle sharing, 20 of the HIV negative IDUs were classified as highly exposed HIV seronegatives (HESNs), 68 as non-HESNs and 85 as unexposed. The control group consisting of 497 blood donors tested negative for all three viruses. TLR3 rs3775291 were determined by using TaqMan Allelic Discrimination Assay.ResultsThe TLR3 rs3775291 T allele frequency was similar among the HIV negative and HIV positive IDUs and blood donors – 36%, 31% and 34%, respectively. The frequency of persons possessing at least one TLR3 rs3775291 T allele was significantly higher in HESNs compared with blood donors and HIV positive IDUs (80% vs. 55%; p = 0.037 and 80% vs. 53%; p = 0.031, respectively). In the univariate analysis, persons who possessed at least one T allele had reduced odds of being HIV seropositive (OR = 0.29, 95% CI = 0.09–0.90). This association remained significant (OR = 0.25, 95% CI = 0.07–0.87) after the adjustment for other co-variates (HCV, HBV serostatus and duration of intravenous drug use).ConclusionsThe TLR3 rs3775291 T allele has a protective effect against HIV infection among HESNs IDUs.     

Factors affecting the causality assessment of adverse events following immunisation in paediatric clinical trials: An online survey

BackgroundSerious adverse events (SAEs) in clinical trials require reporting within 24 h, including a judgment of whether the SAE was related to the investigational product(s). Such assessments are an important component of pharmacovigilance, however classification systems for assigning relatedness vary across study protocols. This on-line survey evaluated the consistency of SAE causality assessment among professionals with vaccine clinical trial experience.MethodsMembers of the clinical advisory forum of experts (CAFÉ), a Brighton Collaboration online-forum, were emailed a survey containing SAEs from hypothetical vaccine trials which they were asked to classify. Participants were randomised to either two classification options (related/not related to study immunisation) or three options (possibly/probably/unrelated). The clinical scenarios, were (i) leukaemia diagnosed 5 months post-immunisation with a live RSV vaccine, (ii) juvenile idiopathic arthritis (JIA) 3 months post-immunisation with a group A streptococcal vaccine, (iii) developmental delay diagnosed at age 10 months after infant capsular group B meningococcal vaccine, (iv) developmental delay diagnosed at age 10 months after maternal immunisation with a group B streptococcal vaccine.ResultsThere were 140 respondents (72 two options, 68 three options). Across all respondents, SAEs were considered related to study immunisation by 28% (leukaemia), 74% (JIA), 29% (developmental delay after infant immunisation) and 42% (developmental delay after maternal immunisation). Having only two options made respondents significantly less likely to classify the SAE as immunisation-related for two scenarios (JIA p = 0.0075; and maternal immunisation p = 0.045). Amongst study investigators (n = 43) this phenomenon was observed for three of the four scenarios: (JIA p = 0.0236; developmental delay following infant immunisation p = 0.0266; and developmental delay after maternal immunisation p = 0.0495).ConclusionsSAE causality assessment is inconsistent amongst study investigators and can be influenced by the classification systems available to them. There is a pressing need for SAE classification systems to be standardised across study protocols.     

Interest in an Ebola vaccine among a U.S. national sample during the height of the 2014–2016 Ebola outbreak in West Africa

To better understand the association between Ebola-related attitudes and interest in receiving an Ebola virus vaccine, a survey was administered to a U.S. national sample using GfK’s KnowledgePanel®. Among participants (N = 1417), 34.1% expressed interest in an Ebola vaccine for themselves. In the subset of participants with children aged 0–17 (N = 410), 38.1% expressed interest in an Ebola vaccine for their child. In multivariable analyses, vaccine interest for oneself was associated with perceived susceptibility to Ebola (p = 0.009), beliefs that the U.S. government should spend money to control Ebola (p = 0.002), and beliefs Ebola posed a national threat (p = 0.007). Vaccine interest for one’s child was associated with perceived severity of Ebola (p = 0.018) and beliefs that the U.S. government should spend money to control Ebola (p = 0.003). Findings highlight the influence of personal and national threat beliefs on vaccine interest. Understanding the impact of threat beliefs may benefit vaccine campaign development during future pandemic threats.     

AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period

BackgroundEliciting durable humoral immunity with sufficient breadth and magnitude is important for HIV-1 vaccine design. The HVTN 114 vaccine trial evaluated different boost regimens administered after a 7-year rest period in participants previously enrolled in HVTN 205, who received either three MVA/HIV62B (MMM) or two DNA and two MVA/HIV62B (DDMM) injections; both vaccines expressed multiple HIV-1 antigens in non-infectious virus-like-particles. The primary objective of HVTN 114 was to assess the impact of a heterologous gp120 protein AIDSVAX B/E boost on the magnitude, breadth and durability of vaccine-induced immune responses.MethodsWe enrolled 27 participants from HVTN 205 into five groups. Eight participants who previously received MMM were randomized and boosted with either MVA/HIV62B alone (T1; n = 4) or MVA/HIV62B and AIDSVAX B/E (T2; n = 4). Nineteen participants who received DDMM were randomized and boosted with MVA/HIV62B alone (T3; n = 6), MVA/HIV62B and AIDSVAX B/E (T4; n = 6), or AIDSVAX B/E alone (T5; n = 7). Boosts were at months 0 and 4. Participants were followed for safety and immunogenicity for 10 months and were pooled for analysis based on the regimen: MVA-only (T1 + T3), MVA + AIDSVAX (T2 + T4), and AIDSVAX-only (T5).ResultsAll regimens were safe and well-tolerated. Prior to the boost vaccination, binding antibody and CD4+T-cell responses were observed 7 years after HVTN 205 vaccinations. Late boosting with AIDSVAX, with or without MVA, resulted in high binding antibody responses to gp120 and V1V2 epitopes, with increased magnitude and breadth compared to those observed in HVTN 205. Late boosting with MVA, with or without AIDSVAX, resulted in increased gp140 and gp41 antibody responses and higher CD4+T-cell responses to Env and Gag.ConclusionsLate boosting with AIDSVAX, alone or in combination with MVA, can broaden binding antibody responses and increase T-cell responses even years following the original MVA/HIV62B with or without DNA-priming vaccine.     

Promoting Tdap immunization in pregnancy: Associations between maternal perceptions and vaccination rates

ObjectiveTdap vaccine uptake among US pregnant women is low despite current recommendations. This study evaluated if a Tdap vaccine information statement (VIS) affected overall perception, vaccination intention, and components of a health behavior model associated with Tdap vaccination rates.MethodsA randomized, prospective study was conducted among pregnant women receiving care at two women's clinics in May–August 2014. Verbally consented participants were randomized to receive either the standard CDC Tdap VIS (sVIS) or a modified version (mVIS) before completing the first multi-part survey (T1). After T1, participants read their assigned VIS then completed the second part (T2). A 2015 chart review identified vaccinated participants. A health behavior model was hypothesized using the Reasoned Action Approach and Health Belief Model. Logistic regression, path analysis, and chi-square tests were used in the analysis.Results279 surveys were analyzed. Average age of the participants was 26.4 years (SD = 5.7) with average gestational age of 25.9 weeks (SD = 9.2). 13% self-reported receiving Tdap vaccine prior to the survey. Overall perception scores significantly increased (3.1–3.4, p < 0.001) after VIS review. A chart review showed that 131 (47%) received the vaccine post study. There was no significant difference in vaccination rates between the sVIS and mVIS groups (45% vs. 49%). Perceived benefits (B = 0.315) and self-efficacy (B = 0.197) were positively associated with the overall perception (T1), while perceived barriers (B = −0.191) were negatively associated with the overall perception (T1). Social norms (B = 0.230), self-efficacy (B = 0.213), and perceived benefits (B = 0.117) were positively associated with vaccination intention (T1). The vaccination intention (T2) was positively associated with participants’ decision to receive Tdap vaccine (B = 0.223).ConclusionA VIS improved overall perception of the Tdap vaccine. Vaccination intention was a predictor of Tdap vaccination. It is crucial to provide information about immunization benefits to promote maternal Tdap vaccination.     

Adolescent confidence in immunisation: Assessing and comparing attitudes of adolescents and adults

IntroductionThere is limited knowledge of adolescent views and attitudes towards immunisation. Our study investigated adolescent attitudes to immunisation and compared differences in vaccination attitudes between adolescents and adults.MethodsThis study was a cross-sectional, national online survey. Recruitment was stratified by state and gender to ensure findings were nationally representative. Regression analyses were performed to assess and compare adolescent and adult views on vaccine benefits, community protection, risks, side effects, sources of information, and decision-making preference.ResultsIn 2013, 502 adolescents and 2003 adults completed the online survey. Lower levels of vaccine confidence were observed in adolescents with adolescents less likely to believe vaccines are beneficial and/or safe compared to adults (p = 0.043). Compared to females, males were less confident of vaccine benefits (p < 0.05) but less concern about vaccine side effects (p < 0.05). Adolescents were more concerned about vaccine side effects than adults for pain (p < 0.001), redness or swelling (p < 0.001), and fever (p = 0.006). Adolescents were less likely than adults to consider health professionals (p < 0.001) and the media (e.g. internet) (p = 0.010) as important sources of information, and were more likely to seek information from social networks (p < 0.001) including families and schools. Although 62.0% of adolescents agreed that parents should make the decision about vaccination for them, adolescents were more likely to prefer a joint decision with parents (p < 0.001) or by themselves (p = 0.007) compared with adults.ConclusionAdolescents have a lesser understanding of vaccine safety and benefits than adults and have higher concerns about potential vaccine reactions. Improving adolescent awareness and knowledge of the benefits and risks of vaccination through school-based educational programs may improve confidence in and uptake of vaccines for adolescents and increase vaccine confidence in the next generation of parents.     

Smoking and mortality among persons aged 75–94

ObjectivesExamine the effect of current level of smoking and lifetime tobacco consumption on mortality in persons 75–94 years of age.MethodsData were from a representative sample of older Jewish persons in Israel, which included 1,200 self-respondent participants aged 75–94 (Mean = 83.1, SD = 5.3) from the Cross-Sectional and Longitudinal Aging Study (CALAS). Data collection took place during 1989–1992. Mortality data on 95.1% of the sample at 20-year follow up were recorded from the Israeli National Population Registry.ResultsThe following variables adversely affected mortality for the whole sample: Smoking 11–20 cigarettes daily (HR = 1.276, p < .05), smoking over 20 cigarettes daily (HR = 1.328, p < .05), total tobacco consumption (HR = 1.002, p < .01), and heavy lifetime tobacco consumption (HR = 1.270, p < .01). Results were similar for persons aged 75–84, but the effect of smoking seems to decrease or disappear for ages 85 and above.ConclusionThis is the first report of all-cause mortality risk in both genders of a representative population aged 75 and over. Increased mortality risk is related to high daily quantity of current smoking, and to cumulative amount of lifetime smoking. The effect of smoking may disappear for ages 85 and above, and should be studied in larger oldest–old samples.     

Pneumococcal vaccination in patients with systemic lupus erythematosus: A multicenter placebo-controlled randomized double-blind study

BackgroundInvasive pneumococcal disease and respiratory tract infections are both frequent and severe in patients with systemic lupus erythematosus (SLE). This study aimed to compare the immunological efficacy and safety of pneumococcal vaccination with the 23-valent polysaccharide (PPS) vaccine alone to a sequential immunization with the 7-valent pneumococcal conjugate (PnCj) vaccine followed by PPS in patients with SLE and stable diseaase.MethodsMulticenter randomized placebo-controlled double-blind trial: PPS vaccine alone (placebo-PPS group) or PnCj vaccine followed by PPS vaccine (PnCj-PPS group) 24 weeks later. The primary endpoint was the rate of responders at week 28 to at least 5 of the 7 serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) shared by both PPS and PnCj. Pneumococcal IgG antibodies’ opsonophagocytic activity (OPA) were also assessed.ResultsTwenty-five patients in the placebo-PPS group and 17 in the PnCj-PPS group were included in a modified intention-to-treat analysis. The primary endpoint was reached in 72% (18/25) in the placebo-PPS and 76% (13/17) in the PnCj-PPS group (p = 0.75). There was no difference in the rates of responders with OPA. At week 52, 13/18 (72%) patients in the placebo-PPS group and 10/13 (77%) patients in the PnCj-PPS group (p = 0.77) that met the primary endpoint at week 28 were still responders to ≥5/7 serotypes shared by both PPS and PnCj vaccines. Nine SLE flares were reported in 6 patients (4 in the placebo-PPS and 2 in the PnCj-PPS groups respectively, p = 0.70).ConclusionSequential administration of PnCj vaccine followed by PPS vaccine is safe and shows short-term immunological efficacy in patients with SLE but was not superior to the PPS vaccine alone.Trial registration: www.clinicaltrials.gov, NCT NCT00611663     

The likelihood of participation in clinical trials can be measured: the Clinical Research Involvement Scales

ObjectiveWe developed the Clinical Research Involvement Scales (CRIS) to assess the willingness to participate in a clinical trial.Study Design and SettingDiverse populations (N = 919) aged 18 years or older from Atlanta, Georgia, were included in comprehensive testing of the 41-item CRIS instrument. The formative phase focused on item content for the new measures (n = 54). Questionnaires from potential vaccine trial participants (n = 865), collected at multiple time points, resulted in the evaluation of scale reliability and validity (i.e., attitudes, behavioral and normative beliefs, perceived social support for clinical research participation, social norm compliance, perceptions of the clinical research organization, and perceived relevance of the research endeavor).ResultsQualitative testing revealed adequate comprehension and content validity of the initial item set. The subjective norms domain (n = 3) initially exhibited poor internal consistency in pilot testing (Cronbach's α = 0.525); yet, rewording of the items resulted in consistently stable measurement improvement (Cronbach's α = 0.850). Each of the CRIS subscales demonstrated extremely high reliability, ranging from 0.734 to 0.918. Confirmatory factor analysis verified item–factor relationships and determined construct and convergent validity (root mean square error of approximation = 0.068; comparative fit index = 0.835).ConclusionsCRIS is a reliable instrument for measuring community attitudes toward participation in biomedical research studies. Results of this study support the use of these scales to recruit diverse populations to clinical trials.