Description: Publication date: Available online 26 December 2014 Source: Vaccine Author(s): Jianhua Le , Edward J. Orff , Andrew A. Fulvini , Liling Huang , Shiroh Onodera , Barbara A. Pokorny , Andrew Malewicz , Patricia Primakov , Doris J. Bucher A critical step in producing the annual inactivated influenza vaccine is the development of high yield (hy) seed viruses by reassortment for improved growth in ovo . Although hy reassortants for type A influenza viruses have been developed for many years, hy B influenza reassortant virus development for vaccine production has proven difficult. In this study, we have developed fourteen hy influenza type B reassortants as vaccine candidate strains with B/Lee/40 as the donor virus. Upon characterization by the Influenza Division at the Centers for Disease Control and Prevention (CDC) and the verification of HA by sequencing, all B reassortants were found to be antigenically indistinguishable from the wild type (wt) parents and suitable for vaccine production. However, only one hy reassortant seed virus from this group was used by a manufacturer for vaccine production. In general, hy reassortants showed an increase in hemagglutination (HA) titers over their wt parents by approximately 8 fold (range 1–32 fold). Gene compositions of the hy B reassortants were analyzed by restriction fragment length polymorphism (RFLP) and the wt origin of the HA and neuraminidase (NA) were confirmed. However, in contrast to hy A reassortants which require the M gene (hy donor A/PR/8/34) for high yield, all fourteen hy B reassortants obtained the NP gene from the hy donor strain (B/Lee/40). The parental source for the remaining genes varied among the hy B reassortants. The results indicate that the B/Lee/40 NP and PB1 gene segments are important contributors to high yield growth in influenza B reassortant viruses for both Yamagata and Victoria lineages. The B/Lee/40 PB2 gene along with wt NS gene also contributed to the improved growth for hy reassortants of Yamagata lineage.

Description: Publication date: Available online 26 December 2014 Source: Vaccine Author(s): Alex Adjagba , Kamel Senouci , Robin Biellik , Batmunkh Nyambat , Pape Coumba Faye , Antoine Durupt , Bradford D. Gessner , Alfred da Silva To empower governments to formulate rational policies without pressure from any group, and to increase the use of evidence-based decision-making to adapt global recommendations on immunization to their local context, the WHO has recommended on multiple occasions that countries should establish National Immunization Technical Advisory Groups (NITAGs). The World Health Assembly (WHA) reinforced those recommendations in 2012 when Member States endorsed the Decade of Vaccines Global Vaccine Action Plan (GVAP). NITAGs are multidisciplinary groups of national experts responsible for providing independent, evidence-informed advice to health authorities on all policy-related issues for all vaccines across all populations. In 2012, according to the WHO–UNICEF Joint Reporting Form, among 57 countries eligible for immunization program financial support from the GAVI Alliance, only 9 reported having a functional NITAG. Since 2008, the Supporting Independent Immunization and Vaccine Advisory Committees (SIVAC) Initiative (at the Agence de Médecine Préventive or AMP) in close collaboration with the WHO and other partners has been working to accelerate and systematize the establishment of NITAGs in low- and middle-income countries. In addition to providing direct support to countries to establish advisory groups, the initiative also supports existing NITAGs to strengthen their capacity in the use of evidence-based processes for decision-making aligned with international standards. After 5 years of implementation and based on lessons learned, we recommend that future efforts should target both expanding new NITAGs and strengthening existing NITAGs in individual countries, along three strategic lines: (i) reinforce NITAG institutional integration to promote sustainability and credibility, (ii) build technical capacity within NITAG secretariats and evaluate NITAG performance, and (iii) increase networking and regional collaborations. These should be done through the development and dissemination of tools and guidelines, and information through a variety of adapted mechanisms.

Description: Publication date: Available online 23 December 2014 Source: Vaccine Author(s): Stéphane Verguet , Mira Johri , Shaun K. Morris , Cindy L. Gauvreau , Prabhat Jha , Mark Jit Background The Measles & Rubella Initiative, a broad consortium of global health agencies, has provided support to measles-burdened countries, focusing on sustaining high coverage of routine immunization of children and supplementing it with a second dose opportunity for measles vaccine through supplemental immunization activities (SIAs). We estimate optimal scheduling of SIAs in countries with the highest measles burden. Methods We develop an age-stratified dynamic compartmental model of measles transmission. We explore the frequency of SIAs in order to achieve measles control in selected countries and two Indian states with high measles burden. Specifically, we compute the maximum allowable time period between two consecutive SIAs to achieve measles control. Results Our analysis indicates that a single SIA will not control measles transmission in any of the countries with high measles burden. However, regular SIAs at high coverage levels are a viable strategy to prevent measles outbreaks. The periodicity of SIAs differs between countries and even within a single country, and is determined by population demographics and existing routine immunization coverage. Conclusions Our analysis can guide country policymakers deciding on the optimal scheduling of SIA campaigns and the best combination of routine and SIA vaccination to control measles.

Description: Publication date: Available online 19 December 2014 Source: Vaccine Author(s): Marien González-Lorenzo , Alessandra Piatti , Liliana Coppola , Maria Gramegna , Vittorio Demicheli , Alessia Melegaro , Marcello Tirani , Elena Parmelli , Francesco Auxilia , Lorenzo Moja Background Health policy makers often have to face decisions on whether and how to incorporate new vaccines into immunisation plans. This study aims to review and catalogue the relevant current frameworks and taxonomies on vaccines and connect these to the DECIDE Evidence to Decision framework (EtD), a general framework based on evidence-based criteria to guide decision-making on intervention adoption. Methods We systematically searched MEDLINE, EMBASE, Cochrane Library and funding agency websites from 1990 to 2013. We included systematic reviews and primary studies presenting decision-making tools for community vaccine adoption. We qualitatively summarised the reports by purpose, targeted country, principal results, and decisional models. We then extracted and compared the dimensions adopted by vaccine frameworks across studies. Results Fourteen studies (five systematic reviews and nine primary studies) were included. Several factors frequently influenced decision-makers’ views on vaccines: the most frequent political-context factors considered were Importance of illness or problem, Vaccine characteristics, Resource use , and Feasibility . Others such as Values and preferences and Acceptability were less consistently reported. We did not find evidence on the reasons why a framework for vaccine adoption differs from that for decisions on the adoption of an intervention in general, such as the EtD. There are limited data on how dimensions are explained in practical factors and directly linked to coverage decisions. Conclusions This review summarises conceptual models and taxonomy of a heterogeneous and evolving area in health policy decisions. A shared and comprehensive framework on vaccine coverage remains to be achieved with its single dimensions (epidemiologic, effectiveness, economic, and social) valued differently across studies. A generic tool such as the EtD conceptualises all relevant dimensions, and might reduce inconsistencies.

Description: Publication date: Available online 17 December 2014 Source: Vaccine Author(s): T.J.D. Knight-Jones , A.N. Bulut , S. Gubbins , K.D.C. Stärk , D.U. Pfeiffer , K.J. Sumption , D.J. Paton Despite years of biannual mass vaccination of cattle, foot-and-mouth disease (FMD) remains uncontrolled in Anatolian Turkey. To evaluate protection after mass vaccination we measured post-vaccination antibodies in a cohort of cattle (serotypes O, A and Asia-1). To obtain results reflecting typical field protection, participants were randomly sampled from across Central and Western Turkey after routine vaccination. Giving two-doses one month apart is recommended when cattle are first vaccinated against FMD. However, due to cost and logistics, this is not routinely performed in Turkey, and elsewhere. Nested within the cohort, we conducted a randomised trial comparing post-vaccination antibodies after a single-dose versus a two-dose primary vaccination course. Four to five months after vaccination, only a third of single-vaccinated cattle had antibody levels above a threshold associated with protection. A third never reached this threshold, even at peak response one month after vaccination. It was not until animals had received three vaccine doses in their lifetime, vaccinating every six months, that most (64% to 86% depending on serotype) maintained antibody levels above this threshold. By this time cattle would be >20 months old with almost half the population below this age. Consequently, many vaccinated animals will be unprotected for much of the year. Compared to a single-dose, a primary vaccination course of two-doses greatly improved the level and duration of immunity. We concluded that the FMD vaccination programme in Anatolian Turkey did not produce the high levels of immunity required. Higher potency vaccines are now used throughout Turkey, with a two-dose primary course in certain areas. Monitoring post-vaccination serology is an important component of evaluation for FMD vaccination programmes. However, consideration must be given to which antigens are present in the test, the vaccine and the field virus. Differences between these antigens affect the relationship between antibody titre and protection.

Description: Publication date: Available online 24 December 2014 Source: Vaccine Author(s): Kirsty Le Doare , Lauren Allen , Beate Kampmann , Paul Trafford Heath , Stephen Taylor , Anneke C. Hesseling , Andrew Gorringe , Christine Elizabeth Jones Background HIV-exposed uninfected infants have increased infection risk and mortality compared to HIV-unexposed infants. HIV-exposed infants may be at increased risk of invasive GBS disease due to reduced maternal antibody against GBS. Methods We quantified antibodies that bind to the surface of whole group B streptococcus (GBS) of serotypes Ia, Ib, II, III and V using novel flow cytometry assays in South African HIV-infected and non-infected mothers and their uninfected infants. Antibody-mediated complement C3b/iC3b deposition onto GBS of these serotypes was also quantified by a novel flow cytometry assay. Results Geometric mean concentration (GMC) of both surface-binding anti-GBS antibody and antibody-mediated complement deposition onto GBS were reduced in HIV-infected women ( n = 46) compared to HIV-uninfected women ( n = 58) for ST1a (surface-binding: 19.3 vs 29.3; p = 0.003; complement deposition: 2.9 vs 5.3 SU/mL; p = 0.003), STIb (24.9 vs 47.6; p = 0.003; 2.6 vs 4.9 SU/mL; p = 0.003), STII (19.8 vs 50.0; p = 0.001; 3.1 vs 6.2 SU/mL; p = 0.001), STIII (27.8 vs 60.1; p = 0.001; 2.8 vs 5.3 SU/mL; p = 0.001) and STV (121.9 vs 185.6 SU/mL; p 〈 0.001) and in their infants for STIa (complement deposition 9.4 vs 27.0 SU/mL; p = 0.02), STIb (13.4 vs 24.5 SU/mL; p = 0.02), STII (14.6 vs 42.7 SU/mL; p = 0.03), STIII (26.6 vs 62.7 SU/mL; p = 0.03) and STV (90.4 vs 165.8 SU/mL; p = 0.04). Median transplacental transfer of antibody from HIV-infected women to their infants was reduced compared to HIV-uninfected women for GBS serotypes II (0.42 [IQR 0.22–0.59] vs 1.0 SU/mL [0.42–1.66]; p 〈 0.001), III (0.54 [0.31–1.03] vs 0.95 SU/mL [0.42–3.05], p = 0.05) and V (0.51 [0.28–0.79] vs 0.75 SU/mL [0.26–2.9], p = 0.04). The differences between infants remained significant at 16 weeks of age. Conclusions Maternal HIV infection was associated with lower anti-GBS surface binding antibody concentration and antibody-mediated C3b/iC3b deposition onto GBS bacteria of serotypes Ia, Ib, II, III and V. This may render these infants more susceptible to early and late onset GBS disease.

Description: Publication date: Available online 19 December 2014 Source: Vaccine Author(s): Swaib Abubaker Lule , Patrice A. Mawa , Gyaviira Nkurunungi , Margaret Nampijja , Dennison Kizito , Florence Akello , Lawrence Muhangi , Alison M. Elliott , Emily L. Webb Background BCG is used widely as the sole licensed vaccine against tuberculosis, but it has variable efficacy and the reasons for this are still unclear. No reliable biomarkers to predict future protection against, or acquisition of, TB infection following immunisation have been identified. Lessons from BCG could be valuable in the development of effective tuberculosis vaccines. Objectives Within the Entebbe Mother and Baby Study birth cohort in Uganda, infants received BCG at birth. We investigated factors associated with latent tuberculosis infection (LTBI) and with cytokine response to mycobacterial antigen at age five years. We also investigated whether cytokine responses at one year were associated with LTBI at five years of age. Methods Blood samples from age one and five years were stimulated using crude culture filtrates of Mycobacterium tuberculosis in a six-day whole blood assay. IFN-γ, IL-5, IL-13 and IL-10 production was measured. LTBI at five years was determined using T-SPOT.TB ® assay. Associations with LTBI at five years were assessed using multivariable logistic regression. Multiple linear regression with bootstrapping was used to determine factors associated with cytokine responses at age five years. Results LTBI prevalence was 9% at age five years. Only urban residence and history of TB contact/disease were positively associated with LTBI. BCG vaccine strain, LTBI, HIV infection, asymptomatic malaria, growth z-scores, childhood anthelminthic treatment and maternal BCG scar were associated with cytokine responses at age five. Cytokine responses at one year were not associated with acquisition of LTBI by five years of age. Conclusion Although multiple factors influenced anti-myocbacterial immune responses at age five, factors likely to be associated with exposure to infectious cases (history of household contact, and urban residence) dominated the risk of LTBI.

Description: Publication date: 15 January 2015 Source: Vaccine, Volume 33, Issue 4 Author(s): Robert H. Hall , David A. Sack Orally-administered cholera vaccine (OCV) has been increasingly examined as an additional tool to intervene against endemic and epidemic cholera. In 2013, short- and long-term field experience with OCV under nine distinctive field settings was reported from India, Bangladesh, Vietnam, Guinea, Haiti, and Thailand. Lead investigators from each of these projects presented their findings at a symposium chaired by Drs. David A. Sack and Robert H. Hall at the Vaccines for Enteric Diseases (VED) Conference in Bangkok on November 7, 2013. The objective of the symposium was to describe the unique features of each setting and project, share field experience of implementing cholera vaccination, discuss results, and identify constraints to the wider use of OCV. The VED provided a forum where >200 attendees engaged with this exciting and potentially decisive new development in the cholera field.

Description: Publication date: 15 January 2015 Source: Vaccine, Volume 33, Issue 4 Author(s): Arwen F. Altenburg , Guus F. Rimmelzwaan , Rory D. de Vries Since inactivated influenza vaccines mainly confer protective immunity by inducing strain-specific antibodies to the viral hemagglutinin, these vaccines only afford protection against infection with antigenically matching influenza virus strains. Due to the continuous emergence of antigenic drift variants of seasonal influenza viruses and the inevitable future emergence of pandemic influenza viruses, there is considerable interest in the development of influenza vaccines that induce broader protective immunity. It has long been recognized that influenza virus-specific CD8 + T cells directed to epitopes located in the relatively conserved internal proteins can cross-react with various subtypes of influenza A virus. This implies that these CD8 + T cells, induced by prior influenza virus infections or vaccinations, could afford heterosubtypic immunity. Furthermore, influenza virus-specific CD4 + T cells have been shown to be important in protection from infection, either via direct cytotoxic effects or indirectly by providing help to B cells and CD8 + T cells. In the present paper, we review the induction of virus-specific T cell responses by influenza virus infection and the role of virus-specific CD4 + and CD8 + T cells in viral clearance and conferring protection from subsequent infections with homologous or heterologous influenza virus strains. Furthermore, we discuss vector-based vaccination strategies that aim at the induction of a cross-reactive virus-specific T cell response.

Description: Publication date: 15 January 2015 Source: Vaccine, Volume 33, Issue 4 Author(s): Pedro L. Moro , Yenlik Zheteyeva , Paige Lewis , Jing Shi , Xin Yue , Oidda I. Museru , Karen Broder Background In 2006, quadrivalent human papillomavirus (HPV4; Gardasil, Merck & Co., Inc.) vaccine was licensed in the US for use in females aged 9–26 years. HPV4 is not recommended during pregnancy; however, inadvertent administration during pregnancy may occur. Objectives To evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received HPV4 vaccine and assess for potentially concerning adverse events among non-manufacturer reports. Methods We searched the VAERS database for non-manufacturer reports of adverse events (AEs) in pregnant women who received HPV4 vaccine from 6/1/2006 to 12/31/2013. We conducted clinical review of reports and available medical records. Results We found 147 reports after HPV4 vaccine administered to pregnant women. The most frequent pregnancy-specific AE was spontaneous abortion in 15 (10.2%) reports, followed by elective terminations in 6 (4.1%). Maternal fever was the most frequent non-pregnancy-specific AE in 3 reports. Two reports of major birth defects were received. No maternal deaths were noted. One hundred-three (70.1%) reports did not describe an AE. Conclusions This review of VAERS non-manufacturer reports following vaccination with HPV4 in pregnancy did not find any unexpected patterns in maternal or fetal outcomes.