2164-5515 Human Vaccines vaccines Austin, Tx Landes Bioscience monthly January 2005 - http://dx.doi.org/10.4161/hv http://www.landesbioscience.com/journals/vaccines/ 2164-5515 Federico Martinón-Torres Nazareth Martinón-Torres Marta Bouzón Alejandro Lorenzo Redondo Collazo Sonia Pértega-Díaz María Teresa Seoane-Pillado Jorge Aboal Viñas and María San-Martín vaccines Acute gastroenteritis hospitalizations among children aged < 5 years before and after introduction of rotavirus vaccines: A hospital-based surveillance study in Galicia, Spain Landes Bioscience 2012-07-01 946 - 952 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Rotavirus vaccines were licensed in Spain between late 2006 and early 2007. Rotavirus vaccination was recommended but not reimbursed by the Spanish National Health System. Significant coverage rates have been reached in Galicia, with an average of 47% since the period July 2007–June 2008. We aim to explore eventual variations in the incidence of hospitalizations for acute gastroenteritis (AGE) among children < 5 y of age before and after vaccine introduction. The annual and monthly hospitalization rates for rotavirus-related AGE and all cause AGE, before and after rotavirus vaccine introduction, were calculated by using the official surveillance system for hospital data. The annual hospitalization rates for rotavirus-related AGE in children < 5 y of age decreased by 14.8% for the period July 2008 to June 2009 and by 44.5% for the period July 2009 to June 2010 as compared with the median rate of the pre-vaccination period (July 2003 to June 2007). The corresponding decreases for all cause AGE were 29.9% and 49.0%, respectively. In children < 12 mo of age a more marked decrease was observed. Compared with pre-vaccination years, a decrease in rotavirus-related and all cause AGE hospitalization rates was observed, with a greater decline in the July 2009 to June 2010 period. http://dx.doi.org/10.4161/hv.20178 http://www.landesbioscience.com/journals/vaccines/article/20178/ article Research Paper 2164-5515 Denice Spero Nikolai Petrovsky and Annie S. De Groot vaccines Report from the field: Fifth vaccine renaissance in Providence RI Landes Bioscience 2012-07-01 1006 - 1009 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience When the next pandemic emerges, will we be ready? Experts say that the number of animal to human ‘species jumps’ is bound to increase as populations increase and the speed of travel between continents accelerates. Typical pandemic timelines no longer apply.1 Pandemic H1N1 traveled the world in just weeks, as did SARS, despite major efforts to contain both outbreaks. The danger of emerging infectious disease to global health is compounded by the potential threat for malevolent bioengineering of existing pathogens and their deliberate dissemination.2 http://dx.doi.org/10.4161/hv.19779 http://www.landesbioscience.com/journals/vaccines/article/19779/ article Commentary 2164-5515 Lamberto Manzoli John P.A. Ioannidis Maria Elena Flacco Corrado De Vito and Paolo Villari vaccines Effectiveness and harms of seasonal and pandemic influenza vaccines in children, adults and elderly: A critical review and re-analysis of 15 meta-analyses Landes Bioscience 2012-07-01 851 - 862 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Fifteen meta-analyses have been published between 1995 and 2011 to evaluate the efficacy/effectiveness and harms of diverse influenza vaccines—seasonal, H5N1 and 2009(H1N1) —in various age-classes (healthy children, adults or elderly). These meta-analyses have often adopted different analyses and study selection criteria. Because it is difficult to have a clear picture of vaccine benefits and harms examining single systematic reviews, we compiled the main findings and evaluated which could be the most reasonable explanations for some differences in findings (or their interpretation) across previously published meta-analyses. For each age group, we performed analyses that included all trials that had been included in at least one relevant meta-analysis, also exploring whether effect sizes changed over time. Although we identified several discrepancies among the meta-analyses on seasonal vaccines for children and elderly, overall most seasonal influenza vaccines showed statistically significant efficacy/effectiveness, which was acceptable or high for laboratory-confirmed cases and of modest magnitude for clinically-confirmed cases. The available evidence on parenteral inactivated vaccines for children aged < 2 y remains scarce. Pre-pandemic “avian” H5N1 and pandemic 2009 (H1N1) vaccines can achieve satisfactory immunogenicity, but no meta-analysis has addressed H1N1 vaccination impact on clinical outcomes. Data on harms are overall reassuring, but their value is diminished by inconsistent reporting. http://dx.doi.org/10.4161/hv.19917 http://www.landesbioscience.com/journals/vaccines/article/19917/ article Review 2164-5515 Eric Sheldon Howard Schwartz Qin Jiang Peter C. Giardina and John L. Perez vaccines A phase 1, randomized, open-label, active-controlled trial to assess the safety of a meningococcal serogroup B bivalent rLP2086 vaccine in healthy adults Landes Bioscience 2012-07-01 888 - 895 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease, but no broadly protective vaccine is yet approved. We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipidated subfamily A and B variants of recombinant LP2086 (rLP2086, also known as factor H binding protein, fHBP). Forty-eight adults, ages 18–40 y, were randomized to receive 60, 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0, 2 and 6 mo. Immunogenicity was assessed by rLP2086-specific immunoglobulin G (IgG) geometric mean titers for subfamily A and B proteins. Safety was determined by laboratory assessments of blood and urine and by reporting of solicited and unsolicited adverse events (AEs). The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels. In each of the four study arms, 11 of the 12 participating subjects reported ≥ 1 AE, and no serious AEs were reported. Local and systemic reactions were mainly mild to moderate. Laboratory abnormalities (including increased sodium, decreased neutrophils, and proteinuria) were not associated with clinical events and were not considered to be related to the study vaccine. Vaccinations were generally well-tolerated. Strong IgG antibody responses and the absence of clinically significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine (www.clinicaltrials.gov; identifier: NCT00879814). http://dx.doi.org/10.4161/hv.19983 http://www.landesbioscience.com/journals/vaccines/article/19983/ article Special Focus Research Paper 2164-5515 Yong Poovorawan Voranush Chongsrisawat Apiradee Theamboonlers Geert Leroux-Roels Priya Diana Crasta and Karin Hardt vaccines Persistence and immune memory to hepatitis B vaccine 20 years after primary vaccination of Thai infants, born to HBsAg and HBeAg positive mothers Landes Bioscience 2012-07-01 896 - 904 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience This study assessed antibody persistence and immune memory to hepatitis B vaccine 20 y after priming with a recombinant hepatitis B virus (HBV) vaccine during infancy. Infants were vaccinated according to a 0, 1, 6 mo schedule with or without simultaneous administration of hepatitis B immunoglobulin (HBIg). Half of the subjects enrolled received an interim booster dose at year 5 (boosted) group, whereas the other half of the subjects enrolled did not (unboosted group). Antibody persistence was assessed until year 20. Immune memory was assessed by administration of a final HBV vaccine challenge dose at year 20 in a second study. At year 20, anti-HBs antibody concentration ≥ 10 mIU/ml rates and GMCs were higher among subjects in the boosted group (84.2% [16/19]; 95%CI: 60.4–96.6) when compared with those in the unboosted group [44.0% (11/25)]; 95% CI: 24.4–65.1). After the HBV vaccine challenge dose at year 20, anti-HBs anamnestic response for subjects in the unboosted and boosted groups was observed in 93.1% (95% CI: 77.2–99.2) and 100% (95% CI: 76.8–100) of subjects, respectively. The mean anti-HBs antibody concentration (GMC) was 562.0 mIU/ml (292.5–1079.7 mIU/ml) post administration of the challenge dose; this is a 28.5 fold increase from the pre- to post-challenge dose administration at year 20. This study demonstrates persistence of anti-HBs antibodies and presence of immune memory following hepatitis B vaccination for up to at least 20 y in Thailand. Immune memory was demonstrated for virtually all subjects, regardless whether they received they had received the additional HBV dose or not. The challenge dose at year 20 was well tolerated and a robust response was demonstrated. ClinicalTrials.gov Identifier: NCT00240526, NCT00774995. http://dx.doi.org/10.4161/hv.19989 http://www.landesbioscience.com/journals/vaccines/article/19989/ article Research Paper 2164-5515 Ghassan Dbaibo Noel Macalalad Mari Rose Aplasca-De Los Reyes Efren Dimaano Véronique Bianco Yaela Baine and Jacqueline M. Miller vaccines The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine: A randomized, controlled non-inferiority study Landes Bioscience 2012-07-01 873 - 880 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ≥ 1:32 in initially seronegative; ≥ 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ≥ 98.0% of subjects had rSBA titers ≥ 1:128. Grade 3 solicited AEs were reported in ≤ 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults. This study is registered at clinicaltrials.gov NCT00453986 http://dx.doi.org/10.4161/hv.20211 http://www.landesbioscience.com/journals/vaccines/article/20211/ article Special Focus Research Paper 2164-5515 Subhash C. Arya and Nirmala Agarwal vaccines Extended coverage of HPV vaccination in middle-aged adults to prevent oropharyngeal cancers Landes Bioscience 2012-07-01 959 - 959 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience http://dx.doi.org/10.4161/hv.20043 http://www.landesbioscience.com/journals/vaccines/article/20043/ article Letter 2164-5515 Carmen L. Pérez Guerra Rosa Rodríguez-Acosta Eunice Soto-Gómez Emily Zielinski-Gutierrez Marisol Peña-Orellana Luis Santiago Reinaldo Rivera R. Rhode Cruz Viani Ramírez Kay Tomashek and Gustavo Dayan vaccines Assessing the interest to participate in a dengue vaccine efficacy trial among residents of Puerto Rico Landes Bioscience 2012-07-01 905 - 915 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Dengue, endemic in Puerto Rico, is a major public health problem. Vaccines are thought the best means to prevent dengue because vector control alone has been largely ineffective. We implemented qualitative studies in 2006 and 2010 to determine the acceptability of conducting placebo-controlled dengue vaccine efficacy trials in Puerto Rican children. Key informant interviews and focus groups with parents and children were conducted in municipalities with high dengue incidence. We used structured open-ended questions to determine motivators and attitudes regarding vaccine trial participation. Knowledge about dengue risk and prevention, and knowledge, attitudes, and beliefs regarding vaccines and vaccine trials were assessed. Using grounded theory, we conducted content analysis and established categories and sub-categories of participant responses. All participants were knowledgeable about dengue prevention and perceived children as most affected age groups. Participants were aware of vaccines benefits and they thought a vaccine could prevent dengue. However, most would not allow their children to participate in a placebo-controlled vaccine trial. Barriers included lack of trust in new vaccines and vaccine trial procedures; fear of developing dengue or side effects from the vaccine and lack of information about candidate dengue vaccines. Participants thought information, including results of previous trials might overcome barriers to participation. Motivators for participation were altruism, protection from dengue, free medical attention, and compensation for transportation and participation. Parents would consider children participation if accurate vaccine trial information is provided. http://dx.doi.org/10.4161/hv.20056 http://www.landesbioscience.com/journals/vaccines/article/20056/ article Research Paper 2164-5515 Emmanuel Feroldi Chitsanu Pancharoen Pope Kosalaraksa Veerachai Watanaveeradej Kerdpanich Phirangkul Maria R. Capeding Mark Boaz Sophia Gailhardou and Alain Bouckenooghe vaccines Single-dose, live-attenuated Japanese encephalitis vaccine in children aged 12–18 months: Randomized, controlled phase 3 immunogenicity and safety trial Landes Bioscience 2012-07-01 929 - 937 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience This trial in 1200 JE-vaccination naïve children (age 12–18 mo) in Thailand and the Philippines aimed to demonstrate consistency of three successive industrial scale manufacturing lots of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) and consistency between industrial scale manufacturing lots and a fourth, development lot. Children received JE-CV from one of three successive industrial scale lots produced in Thailand (n = 899), or from a fourth development lot produced in the USA (n = 199), or hepatitis A control vaccine (n = 102). Antibodies were assessed by 50% plaque reduction neutralization test (PRNT50) at screening and Day 28. Seroconversion rates (titer of < 10 at baseline and ≥ 10 on Day 28, or a four-fold rise from a baseline titer of ≥ 10) were determined per group. Lot-to-lot consistency of seroconversion rate and GMT was demonstrated between the 3 industrial scale lots, and between these lots and the US lot. Seroconversion rate on pooled data 28 d after JE-CV vaccination (Thai lots) was 95.0% [95% confidence interval (CI); 93.3–96.3]. The safety profile of JE-CV was favorable and comparable with hepatitis A vaccine. There were no serious adverse events related to vaccination. This study demonstrated the consistency of three successive industrial scale JE-CV vaccine lots, as well as consistency with a development lot. The study also demonstrated that a single dose of JE-CV is well tolerated and elicits a high protective immune response, seroconverting 95% of JE-naïve Asian children aged 12–18 mo. ClinicalTrials.gov: NCT00735644 http://dx.doi.org/10.4161/hv.20071 http://www.landesbioscience.com/journals/vaccines/article/20071/ article Research Paper 2164-5515 Ramesh Verma Pardeep Khanna and Suraj Chawla vaccines Inactivated polio vaccine: Time to introduce it in India’s national immunization schedule Landes Bioscience 2012-07-01 956 - 958 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Polio is a communicable disease caused by poliovirus that may attack nerve cells of the brain and spinal cord. The victims develop neurological complications, likes stiffness of the neck, muscular weakness, or paralysis of one or more limbs. In severe cases, it may be fatal due to respiratory paralysis. The world has seen tremendous gains in polio eradication over the past year. India and Nigeria saw a reduction in cases of almost 95% from 2009 to 2010, and cases of wild poliovirus type 3 (WPV3) fell by 92% globally over the same period. In fact, no case has been reported in India since February 2011, such that India may be on the verge of eradicating polio. Nevertheless, polio control experts are particularly worried about Vaccine-Derived Poliovirus (VDPV). Global surveillance efforts picked up 430 cases of VDPV from several countries between July 2009 and March 2011. In India, 7 cases of VDPV were reported during the year 2011. As long as OPV is used, virologists say that the world is at risk of VDPV causing polio in unprotected children. Achieving a polio-free world will require the “cessation of all OPV” and with it the elimination of the risk of vaccine-associated paralytic polio (VAPP) or VDPV infections. To this effect, in 2011 the Global Polio Eradication Initiative (GPEI) will produce and develop a new roadmap for VDPV Elimination. Several countries have shifted from all OPV to sequential OPV-IPV schedules and all-IPV schedules with elimination of live poliovirus. IPV will be indispensable in the post-eradication era when use of OPV has to stop but “vaccination against polio” cannot stop. IPV offers complete individual protection and has been considered as an additional tool at present for those who can afford the vaccine, and since we are nearing the eradication of polio, it is time to shift from OPV to sequential OPV-IPV schedule in India. Such a strategy will avoid inevitable problems with VAPP. http://dx.doi.org/10.4161/hv.20089 http://www.landesbioscience.com/journals/vaccines/article/20089/ article Commentary 2164-5515 Suzanne Cremin John F. Menton Lydie Canier Mary Horgan and Liam J. Fanning vaccines The prevalence and genotype of human papillomavirus on cervical samples from an Irish female population with external genital warts Landes Bioscience 2012-07-01 916 - 920 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience The aim of this study was to determine the cervical genotype profile of females who presented to an STI Clinic with external genital warts (EGW); and to determine the potential vaccine coverage prior to the uptake of the HPV vaccines. Sixty-one cervical scrapings were taken from females aged 18–35 y who had external genital warts or a history of external genital warts. The resulting 50 samples that were positive for HPV-DNA were subjected to genotype identification. Forty-six of these samples had detectable genotypes by LIPA analysis and most (78%, 36/46) had multiple low risk (LR) and high risk (HR) genotypes on the cervix. Twenty-five of these samples (54%) had more than 1 HR genotype. Of the 36 patients who had any HR genotypes, 18 (50%) were identified to have the most oncogenic HPV genotypes, namely 16 and 18. Three of these samples had both 16 and 18 on the cervix. The presence of multiple HR genotypes on the majority of cervical samples from a self-referred population of females with EGW is presented. This study is of importance since persistent HR-HPV is the necessary risk factor in the development of precancerous and cancerous lesions of the cervix. Gardisil, the quadrivalent HPV vaccine would have been useful in the prevention of 28% (13/46) of these infections. http://dx.doi.org/10.4161/hv.20122 http://www.landesbioscience.com/journals/vaccines/article/20122/ article Research Paper 2164-5515 Arfa Moshiri Abolfazl Dashtbani-Roozbehani Shahin Najar Peerayeh and Seyed Davar Siadat vaccines Outer membrane vesicle: A macromolecule with multifunctional activity Landes Bioscience 2012-07-01 953 - 955 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Nowadays adjuvants are extensively used as immuno-stimulatory and immuno-modulatory compounds as components of subunit and combination vaccine formulations. The adjuvants of microbial origin are more frequently used among currently used licensed or experimental adjuvants. The outer membrane vesicle (OMV) of Neisseria meningitidis is among the newly studied components of microbial origin, which could be applied as an adjuvant. Although the potency of OMV as a carrier (conjugated to a hapten) is now proven, the adjuvant properties of OMV have particular significance as a potential target for protective immunity. Since it has immune-stimulatory activity, OMV has been utilized in vaccine development. This commentary reviews the different applications of OMV as potential adjuvant in the field of vaccine development. http://dx.doi.org/10.4161/hv.20166 http://www.landesbioscience.com/journals/vaccines/article/20166/ article Commentary 2164-5515 Andres H. Gutiérrez Denice Spero Cyril Gay Mirko Zimic and Anne S. De Groot vaccines New vaccines needed for pathogens infecting animals and humans: One Health Landes Bioscience 2012-07-01 971 - 978 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience The field of “One Health” encourages researchers to collaborate across a wide range of disciplines to improve health at the animal-human-ecosystems interface. One Health recognizes the potential of emerging infectious diseases to impact public health and global food security, and the need for a multidisciplinary approach to counteract the effect of these diseases. Vaccinologists are also beginning to engage in research related to One Health, recognizing that preventing transmission of emerging infectious diseases at the animal-human interface is critically important for protecting the world population from epizootics and pandemics. In this synopsis of recent work in the One Health field, we describe some emerging One Health pathogens, discuss the importance of One Health to food safety and biodefense, propose strategies for improving One Health including the development of new vaccines and new vaccine design approaches, and close with a brief discussion of the opportunities and risks related to One Health vaccine research. http://dx.doi.org/10.4161/hv.20202 http://www.landesbioscience.com/journals/vaccines/article/20202/ article Review 2164-5515 Eva d’Hennezel and Ciriaco A. Piccirillo vaccines Functional plasticity in human FOXP3+ regulatory T cells: Implications for cell-based immunotherapy Landes Bioscience 2012-07-01 1001 - 1005 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience CD4+ regulatory T (Treg) cells expressing the Foxp3 transcription factor are critical for the induction and maintenance of immune homeostasis and self-tolerance in experimental rodents and humans. Foxp3+ Treg cells constitute a unique CD4+ T cell subset with potent suppressive properties, and their functional and homeostatic stability is essential to ensure dominant tolerance in a variety of inflammatory settings. Interestingly, recent evidence points to the inherent potential of Treg cells to adapt to environmental cues and consequently manifest functional plasticity by downregulating Foxp3 expression, and reprogramming into inflammatory T cells. The potential for suppressive Foxp3+ Treg cells to undergo functional plasticity and gain inflammatory properties is of concern when one considers the ex vivo manipulation or generation of such cells for therapeutic purposes in various autoimmune or chronic inflammatory disorders. Collectively, the experimental evidence accumulated so far on the modalities of this plasticity can provide valuable cues as to strategies that can be implemented to control it, potentially allowing to facilitate the path to efficient and safe Treg-based therapy. http://dx.doi.org/10.4161/hv.20203 http://www.landesbioscience.com/journals/vaccines/article/20203/ article Research Paper 2164-5515 Juana María Santos-Sancho Isabel Jimenez-Trujillo Valentín Hernández-Barrera Ana López-de Andrés Pilar Carrasco-Garrido Paloma Ortega-Molina and Rodrigo Jiménez-García vaccines Influenza vaccination coverage and uptake predictors among Spanish adults suffering COPD Landes Bioscience 2012-07-01 938 - 945 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience The aim of this study is to compare influenza vaccination coverage among Spaniards aged 40 y or over who suffer from chronic obstructive pulmonary disease (COPD) with those without this illness to identify the factors that influence vaccination uptake among patients with COPD. Data was extracted from the European Health Survey performed in Spain in 2009/10, and analyzed data on 15,355 Spaniards (≥ 40 y of age), of whom 1,309 (8.2% 95%CI 7.7–8.7) had COPD was used. We considered the answer (yes/no) to the question about whether or not the interviewed person had been vaccinated against influenza in the previous flu season. We used the answer to this question as the dependent variable. For independent variables, we analyzed social demographic characteristics, health related variables, and the utilization of health care services. Vaccination coverage among patients with COPD is 49.4% (95% CI: 46.3–52.5%) and 21.3% (95% CI: 20.7–21.9) among people without (p < 0.001). The probability of being vaccinated is three times greater for COPD patients (crude OR = 3.0, 95% CI: 2.6–3.5). Among COPD patients the uptake of vaccination increased with age. Other factors associated with an increase in vaccination coverage were: being male, perceiving one’s health as fair or poor, not smoking, and having seen a doctor during the previous month. The rate of flu vaccination among adult Spaniards with COPD is lower than desired. Urgent strategies for increasing vaccination coverage are necessary for COPD sufferers aged under 65 of age and those with unhealthy lifestyles. http://dx.doi.org/10.4161/hv.20204 http://www.landesbioscience.com/journals/vaccines/article/20204/ article Research Paper 2164-5515 Mari Rose Aplasca-De Los Reyes Efren Dimaano Noel Macalalad Ghassan Dbaibo Véronique Bianco Yaela Baine and Jacqueline M. Miller vaccines The investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults Landes Bioscience 2012-07-01 881 - 887 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Co-administration of meningococcal serogroups A, C, W-135 and Y conjugate vaccine (ACWY-TT) with seasonal influenza vaccine was investigated in a subset of adults enrolled in a larger study evaluating lot-to-lot consistency of ACWY-TT and non-inferiority to licensed tetravalent meningococcal polysaccharide vaccine (MenPS). Subjects in this sub-study were randomized (3:1:1) to receive ACWY-TT alone (ACWY-TT group) or with seasonal influenza vaccine (Coad), or licensed MenPS alone. Serum bactericidal antibodies (rSBA) and serum haemagglutination-inhibition (HI) antibody titers were measured pre- and 1 mo post-vaccination. Non-inferiority of the Coad group compared with ACWY-TT group was demonstrated in terms of rSBA geometric mean antibody titers (GMTs) to serogroups A, W-135 and Y. For serogroup C the pre-defined non-inferiority limit was marginally exceeded. Post-vaccination rSBA GMTs were significantly higher (exploratory analysis) in the Coad group compared with the MenPS group for serogroups A, W-135, and Y and were similar to the MenPS group for serogroup C. Overall, > 97% of subjects achieved rSBA titers ≥ 1:128 for all serogroups. The Coad group met all criteria defined by the Committee on Human Medicinal Products (CHMP) for seroprotection, seroconversion and seroconversion factor for HI antibodies for all three influenza strains. Grade 3 solicited local/general symptoms were reported by ≤ 1.9% of subjects in any group. These data support the co-administration of ACWY-TT with seasonal influenza vaccine when protection is needed against both diseases. This study is registered at clinicaltrials.gov NCT00453986 http://dx.doi.org/10.4161/hv.20212 http://www.landesbioscience.com/journals/vaccines/article/20212/ article Special Focus Research Paper 2164-5515 Markus Knuf Yaela Baine Véronique Bianco Dominique Boutriau and Jacqueline M. Miller vaccines Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children Landes Bioscience 2012-07-01 866 - 872 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience The present extension study, conducted in children originally vaccinated at 12–14 mo or 3–5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ≥ 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ≥ 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ≥ 1:8 and ≥ 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984. http://dx.doi.org/10.4161/hv.20229 http://www.landesbioscience.com/journals/vaccines/article/20229/ article Special Focus Short Report 2164-5515 Timo Vesikari Aino Forstén Astrid Borkowski Nikolaos Gaitatzis Angelika Banzhoff and Ralf Clemens vaccines Homologous and heterologous antibody responses to a one-year booster dose of an MF59®: Adjuvanted A/H5N1 pre-pandemic influenza vaccine in pediatric subjects Landes Bioscience 2012-07-01 921 - 928 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Background: Primary immunization with two doses of MF59®-adjuvanted A/H5N1 influenza vaccine has been shown to be highly immunogenic and well tolerated in children and adolescents. Assessment of long-term antibody persistence after priming, and the effects of a one-year booster dose in children and adolescents was needed. Objectives This study assessed homologous and heterologous antibody responses to a one-year booster dose of MF59-adjuvanted A/H5N1 influenza vaccine in previously primed children. Subjects and methods: Twelve months after primary vaccination, toddlers, children and adolescents received a single booster dose of the same A/H5N1 vaccine. Paired sera were collected before and three weeks after booster vaccination. Homologous antibody responses against the A/Vietnam/1194/2004 vaccine strain were measured by hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN) assays. Heterologous antibody responses against A/Indonesia/5/2005 and A/Anhui/1/2005 strains were assessed by MN assay only. Results: Twelve months after primary vaccination, persistent, homologous, seroprotective HI antibody titers (≥ 40) were observed in 46%, 26% and 30% of toddlers, children and adolescents; following booster vaccination, seroprotection rates increased to 99%, 98% and 91%, respectively. All toddlers and children, and 99% of adolescents achieved MN antibody titers ≥ 40. Cross-reactive A/H5N1 antibodies were detected in 94–98% of subjects after booster vaccination. Conclusions Two priming doses of MF59-adjuvanted A/H5N1 vaccine resulted in homologous and heterologous antibody responses which persisted for up to one year after immunization. A one-year booster dose was highly immunogenic, generating high homologous and cross-reactive A/H5N1 antibody titers. http://dx.doi.org/10.4161/hv.20248 http://www.landesbioscience.com/journals/vaccines/article/20248/ article Research Paper 2164-5515 Ramon Bencharitiwong Stephanie Leonard Theodore Tsai and Anna Nowak-Węgrzyn vaccines In vitro assessment of the allergenicity of novel MF59-adjuvanted pandemic H1N1 influenza vaccine produced in dog kidney cells Landes Bioscience 2012-07-01 863 - 865 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience A licensed inactivated MF59-adjuvanted seasonal influenza vaccine (Optaflu) produced in canine kidney cells (MDCK 33016-PF) contained no egg proteins and did not trigger degranulation in rat basophilic leukemia (RBL) cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. The cell-derived pandemic H1N1 influenza vaccine was also adjuvanted with the emulsion adjuvant MF59, and support for its similar safe use was sought. We sought to evaluate in vitro allergenicity of the MF59-adjuvanted cell-derived pandemic H1N1 influenza vaccine in subjects with dog allergy, with a mediator release assay. RBL-2H3 cells transfected with human Fcε receptor type 1 were sensitized with sera from adult dog-allergic subjects and stimulated with serial dilutions of pandemic H1N1 influenza vaccine and dog dander extract. β-N-hexosaminidase release (NHR) was used as a marker of RBL degranulation.. Median dog dander-specific IgE in 30 dog-allergic subjects was 27.7 kUA/L (range 10.1; >100); and in 5 dog non-allergic subjects was <0.35 kUA/L (UniCAP system). Median (range) maximum NHR in dog-allergic subjects was: pandemic H1N1 influenza vaccine 1.1% (0; 4.4) and dog dander 6.9% (0.7; 37.3), P < 0.001. In conclusion, MF59-adjuvanted pandemic H1N1 influenza vaccine produced in continuous canine kidney cells did not trigger degranulation in RBL cells passively sensitized with human anti-dog IgE, supporting its safe use in dog-allergic individuals. http://dx.doi.org/10.4161/hv.20324 http://www.landesbioscience.com/journals/vaccines/article/20324/ article Short Report 2164-5515 Anne S. De Groot Lauren Levitz Matthew T. Ardito Gail Skowron Kenneth H. Mayer Soren Buus Christine M. Boyle and William D. Martin vaccines Further progress on defining highly conserved immunogenic epitopes for a global HIV vaccine: HLA-A3-restricted GAIA vaccine epitopes Landes Bioscience 2012-07-01 987 - 1000 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Two major obstacles confronting HIV vaccine design have been the extensive viral diversity of HIV-1 globally and viral evolution driven by escape from CD8+ cytotoxic T-cell lymphocyte (CTL)-mediated immune pressure. Regions of the viral genome that are not able to escape immune response and that are conserved in sequence and across time may represent the “Achilles’ heel” of HIV and would be excellent candidates for vaccine development. In this study, T-cell epitopes were selected using immunoinformatics tools, combining HLA-A3 binding predictions with relative sequence conservation in the context of global HIV evolution. Twenty-seven HLA-A3 epitopes were chosen from an analysis performed in 2003 on 10,803 HIV-1 sequences, and additional sequences were selected in 2009 based on an expanded set of 43,822 sequences. These epitopes were tested in vitro for HLA binding and for immunogenicity with PBMCs of HIV-infected donors from Providence, Rhode Island. Validation of these HLA-A3 epitopes conserved across time, clades, and geography supports the hypothesis that epitopes such as these would be candidates for inclusion in our globally relevant GAIA HIV vaccine constructs. http://dx.doi.org/10.4161/hv.20528 http://www.landesbioscience.com/journals/vaccines/article/20528/ article Research Paper 2164-5515 Hellen Amuguni and Saul Tzipori vaccines <italic>Bacillus subtilis</italic>: A temperature resistant and needle free delivery system of immunogens Landes Bioscience 2012-07-01 979 - 986 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Most pathogens enter the body through mucosal surfaces. Mucosal immunization, a non-invasive needle-free route, often stimulates a mucosal immune response that is both effective against mucosal and systemic pathogens. The development of mucosally administered heat-stable vaccines with long shelf life would therefore significantly enhance immunization programs in developing countries by avoiding the need for a cold chain or systemic injections. Currently, recombinant vaccine carriers are being used for antigen delivery. Engineering Bacillus subtilis for use as a non-invasive and heat stable antigen delivery system has proven successful. Bacterial spores protected by multiple layers of protein are known to be robust and resistant to desiccation. Stable constructs have been created by integration into the bacterial chromosome of immunogens. The spore coat has been used as a vehicle for heterologous antigen presentation and protective immunization. Sublingual (SL) and intranasal (IN) routes have recently received attention as delivery routes for therapeutic drugs and vaccines and recent attempts by several investigators, including our group, to develop vaccines that can be delivered intranasally and sublingually have met with a lot of success. As discussed in this Review, the use of Bacillus subtilis to express antigens that can be administered either intranasally or sublingually is providing new insights in the area of mucosal vaccines. In our work, we evaluated the efficacy of SL and IN immunizations with B. subtilis engineered to express tetanus toxin fragment C (TTFC) in mice and piglets. These bacteria engineered to express heterologous antigen either on the spore surface or within the vegetative cell have been used for oral, IN and SL delivery of antigens. A Bacillus subtilis spore coat protein, CotC was used as a fusion partner to express the tetanus fragment C. B. subtilis spores known to be highly stable and safe are also easy to purify making this spore-based display system a potentially powerful approach for surface expression of antigens. These advances will help to accelerate the development and testing of new mucosal vaccines against many human and animal diseases. http://dx.doi.org/10.4161/hv.20694 http://www.landesbioscience.com/journals/vaccines/article/20694/ article Review 2164-5515 Pierre R. Leblanc Jianping Yuan Tim Brauns Jeffrey A. Gelfand and Mark C. Poznansky vaccines Accelerated vaccine development against emerging infectious diseases Landes Bioscience 2012-07-01 1010 - 1012 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Emerging and re-emerging infectious diseases represent a major challenge to vaccine development since it involves two seemingly contradictory requirements. Rapid and flexible vaccine generation while using technologies and processes that can facilitate accelerated regulatory review. Development in the “-omics” in combination with advances in vaccinology offer novel opportunities to meet these requirements. Here we describe how a consortium of five different organizations from academia and industry is addressing these challenges. This novel approach has the potential to become the new standard in vaccine development allowing timely deployment to avert potential pandemics. http://dx.doi.org/10.4161/hv.20805 http://www.landesbioscience.com/journals/vaccines/article/20805/ article Commentary 2164-5515 Paulo H. Verardi Allison Titong and Caitlin J. Hagen vaccines A vaccinia virus renaissance: New vaccine and immunotherapeutic uses after smallpox eradication Landes Bioscience 2012-07-01 961 - 970 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience In 1796, Edward Jenner introduced the concept of vaccination with cowpox virus, an Orthopoxvirus within the family Poxviridae that elicits cross protective immunity against related orthopoxviruses, including smallpox virus (variola virus). Over time, vaccinia virus (VACV) replaced cowpox virus as the smallpox vaccine, and vaccination efforts eventually led to the successful global eradication of smallpox in 1979. VACV has many characteristics that make it an excellent vaccine and that were crucial for the successful eradication of smallpox, including (1) its exceptional thermal stability (a very important but uncommon characteristic in live vaccines), (2) its ability to elicit strong humoral and cell-mediated immune responses, (3) the fact that it is easy to propagate, and (4) that it is not oncogenic, given that VACV replication occurs exclusively within the host cell cytoplasm and there is no evidence that the viral genome integrates into the host genome. Since the eradication of smallpox, VACV has experienced a renaissance of interest as a viral vector for the development of recombinant vaccines, immunotherapies, and oncolytic therapies, as well as the development of next-generation smallpox vaccines. This revival is mainly due to the successful use and extensive characterization of VACV as a vaccine during the smallpox eradication campaign, along with the ability to genetically manipulate its large dsDNA genome while retaining infectivity and immunogenicity, its wide mammalian host range, and its natural tropism for tumor cells that allows its use as an oncolytic vector. This review provides an overview of new uses of VACV that are currently being explored for the development of vaccines, immunotherapeutics, and oncolytic virotherapies. http://dx.doi.org/10.4161/hv.21080 http://www.landesbioscience.com/journals/vaccines/article/21080/ article Review 2164-5515 Ronald W. Ellis and Eva M. Riedmann vaccines Letter from the Editor Landes Bioscience 2012-07-01 845 - 845 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience http://dx.doi.org/10.4161/hv.21441 http://www.landesbioscience.com/journals/vaccines/article/21441/ article Editor's Corner 2164-5515 Annie S. De Groot vaccines Fifth Vaccine Renaissance introduction Landes Bioscience 2012-07-01 960 - 960 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience http://dx.doi.org/10.4161/hv.21442 http://www.landesbioscience.com/journals/vaccines/article/21442/ article Editor's Corner 2164-5515 Eva M. Riedmann vaccines News Landes Bioscience 2012-07-01 846 - 850 Human Vaccines & Immunotherapeutics 8-7 Landes Bioscience Successful combination: existing drugs boost cancer vaccine responses Inovio's universal avian flu vaccine generates protective antibody responses in phase 1 Update on NewLink’s HyperAcute cancer immunotherapy products Ghana and Rwanda expand national immunization programs News studies: Combining PROSTVAC with conventional cancer therapy Promising phase 1 data for the first "Cross-Kingdom“ vaccine Oral TB vaccine shows promise in phase 2 trial http://dx.doi.org/10.4161/hv.21443 http://www.landesbioscience.com/journals/vaccines/article/21443/ article News, Policy and Profiles