Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Shaun H. Pennington, Daniela M. Ferreira, Jesús Reiné, Tonney S. Nyirenda, Ameeka L. Thompson, Carole A. Hancock, Angela D. Wright, Stephen B. Gordon, Melita A. Gordon Background We have previously demonstrated that polyfunctional Ty21a-responsive CD4 + and CD8 + T cells are generated at the duodenal mucosa 18 days following vaccination with live-attenuated S . Typhi (Ty21a). The longevity of cellular responses has been assessed in peripheral blood, but persistence of duodenal responses is unknown. Methods We vaccinated eight healthy adults with Ty21a. Peripheral blood and duodenal samples were acquired after a median of 1.5 years (ranging from 1.1 to 3.7 years) following vaccination. Cellular responses were assessed in peripheral blood and at the duodenal mucosa by flow cytometry. Levels of IgG and IgA were also assessed in peripheral blood by enzyme-linked immunosorbent assay. Results No T-cell responses were observed at the duodenal mucosa, but CD4 + T-cell responses to Ty21a and FliC were observed in peripheral blood. Peripheral anti-lipopolysaccharide IgG and IgA responses were also observed. Early immunoglobulin responses were not associated with the persistence of long-term cellular immune responses. Conclusions Early T-cell responses which we have previously observed at the duodenal mucosa 18 days following oral vaccination with Ty21a could not be detected at a median of 1.5 years. Peripheral responses were observed at this time. Immunoglobulin responses observed shortly after vaccination were not associated with cellular immune responses at 1.5 years, suggesting that the persistence of cellular immunity is not associated with the strength of the initial humoral response to vaccination.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Amit Saha, Andrew Hayen, Mohammad Ali, Alexander Rosewell, C. Raina MacIntyre, John D. Clemens, Firdausi Qadri Background Evaluations of oral cholera vaccines (OCVs) have demonstrated their effectiveness in diverse settings. However, low vaccine uptake in some settings reduces the opportunity for prevention. This paper identifies the socioeconomic factors associated with vaccine uptake in a mass vaccination program. Methods This was a three-arm (vaccine, vaccine plus behavioral change, and non-intervention) cluster randomized trial conducted in Dhaka, Bangladesh. Socio-demographic and vaccination data were collected from 268,896 participants. A geographical information system (GIS) was used to design and implement the vaccination program. A logistic regression model was used to assess the association between vaccine uptake and socioeconomic characteristics. Results The GIS supported the implementation of the vaccination program by identifying ideal locations of vaccination centres for equitable population access, defining catchment areas of daily activities, and providing daily coverage maps during the campaign. Among 188,206 individuals in the intervention arms, 123,686 (66%) received two complete doses, and 64,520 (34%) received one or no doses of the OCV. The vaccine uptake rate was higher in females than males (aOR: 1.80; 95% CI = 1.75–1.84) and in younger (〈15 years) than older participants (aOR: 2.19; 95% CI = 2.13–3.26). Individuals living in their own house or having a higher monthly family expenditure were more likely to receive the OCV (aOR: 1.60; 95% CI = 1.50–1.70 and aOR: 1.14; 95% CI = 1.10–1.18 respectively). Individuals using treated water for drinking or using own tap as the source of water were more likely to receive the OCV (aOR: 1.23; 95% CI = 1.17–1.29 and aOR: 1.14; 95% CI = 1.02–1.25 respectively) than their counterpart. Vaccine uptake was also significantly higher in participants residing farther away from health facilities (aOR: 95% 1.80; CI = 1.36–2.37). Conclusion The GIS was useful in designing field activities, facilitating vaccine delivery and identifying socioeconomic drivers of vaccine uptake in the urban area of Bangladesh. Addressing these socioeconomic drivers may help improve OCV uptake, thereby effectiveness of the OCV in a community.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Saber Yezli, Philippe Gautret, Abdullah M. Assiri, Bradford D. Gessner, Badriah Alotaibi Meningococcal disease is a serious public health threat given the seriousness of the illness, its disabling sequelae and its potential for epidemic spread. The disease is a concern during mass gatherings which provide conditions that facilitate transmission of infectious agents including Neisseria meningitidis . Implementation of appropriate meningococcal disease preventive measures during at-risk mass gatherings is crucial to prevent illness and outbreaks which may result in significant morbidity and mortality as well as local and international spread of the disease. These preventive measures should be informed by comprehensive risk assessments of the disease at those events and may include the use of vaccination, chemoprophylaxis and health awareness and educational campaigns, supported by efficient disease surveillance and response systems. The Hajj and Umrah religious mass gatherings in the Kingdom of Saudi Arabia are examples of how the implementation of such preventive measures was successful in reducing the incidence of meningococcal disease during these events as well as controlling and preventing outbreaks. Lessons learned from the Hajj and Umrah experience can inform meningococcal disease preventive strategies for other mass gatherings worldwide.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Rachael Biggart, Adam Finn, Robin Marlow Observational studies have linked a reduction in childhood seizures (CS) to the introduction of rotavirus vaccination (RV). England is opportunely placed to explore this due to well-defined introduction, high uptake of RV and centralised Hospital Episodes Statistics recording all admissions. We investigated the association between seizures and vaccine use through interrupted time-series analysis of all CS admissions in children 〈3 years old (ICD-10 codes; G40 ∗ -G41 ∗ , R56.0 ∗ ) during 2007–2017. We did not detect a statistically significant association between the introduction of RV and admission with febrile (p = 0.84), afebrile (p = 0.83) or all CS (p = 0.93), even when limited to peak rotavirus seasonality (March). This is the first ecological study in a country that exclusively uses the monovalent vaccine. Although a negative finding, we would argue that if an effect cannot be detected at this population level then it is unlikely to be clinically or economically significant but generates hypotheses of potential non-specific effects.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Wan Liu, Yik Chun Wong, Samantha M.Y. Chen, Jiansong Tang, Haibo Wang, Allen Ka Loon Cheung, Zhiwei Chen HIV-1 diversity and latent reservoir are the major challenges for the development of an effective AIDS vaccine. It is well indicated that Gag-specific CD8 + T cells serve as the dominant host immune surveillance for HIV-1 control, but it still remains a challenge for vaccine design to induce broader and stronger cytotoxic T cell immunity against the virus. Genetic variation of the HIV-1 gag gene across different clades is one of the reasons for the reduction of antigenic epitope coverage. Here, we report an immunization strategy with heterologous vaccines expressing a mosaic Gag antigen aimed to increase antigenic breadth against a wider spectrum of HIV-1 strains. Priming using a DNA vaccine via in vivo electroporation, followed by boosting with a live replication-competent modified vaccinia TianTan (MVTT) vectored vaccine, elicited greater and broader protective Gag-specific immune responses in mice. Compared to DNA or MVTT homologous immunization, the heterologous DNA/MVTT vaccination resulted in higher frequencies of broadly reactive, Gag-specific, polyfunctional, long-lived cytotoxic CD8 + T cells, as well as increased anti-Gag antibody titer. Importantly, the DNA/MVTT heterologous vaccination induced protection against EcoHIV and mesothelioma AB1-Gag challenges. In summary, the stronger protective Gag-specific immunity induced by the heterologous regimen using two safe vectors shows promise for further development to enhance anti-HIV-1 immunity. Our study has important implications for immunogen design and the development of an effective HIV-1 heterologous vaccination strategy.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Xinyu Liu, Danhua Zhao, Lili Jia, Hongshan Xu, Rui Na, Yonghong Ge, Shaoxiang Liu, Yongxin Yu, Yuhua Li Japanese encephalitis (JE) live attenuated vaccine SA14-14-2 is the most widely used JE vaccine in the world. Large-scale clinical trials have demonstrated satisfactory safety and efficacy profiles. The establishment of genetic and attenuated neurovirulence characteristics and their stabilities of SA14-14-2 virus are important in relation to vaccine safety in humans. Therefore, several researchers have studied and analyzed the full-length gene sequences of the SA14-14-2 virus strain. However, sequencing results have shown a significant difference. Here, we further studied the full-length sequence of three class seed virus banks of the vaccine as well as two vaccine viruses with different passages in primary hamster kidney cells, and compared them with our original stored SA14 parent virus (low passage in mouse brain). The full-length gene sequence determined in this study indicates there were 57 nucleotide and 25 amino acid substitutions of the SA14-14-2 strain compared to its parental SA14 virus strain. The full-length sequences of the three class seed bank viruses and the vaccine virus PHKC8 were completely identical among them, but the working seed virus passaged in primary hamster kidney cells for 17 generations (PHKC17) had a single nucleotide change at the 5′ NCR. Both KM and ICR mice tested by intracerebral (i.c.) or subcutaneous (s.c.) routes with the three class seed viruses and vaccine viruses with ≥5.7 lgpfu/mL remained healthy, but all the mice inoculated with the SA14 parental virus strain died as early as day 5 post-inoculation. The present study provided new information on the full-length gene sequence and attenuated neurovirulence of SA14-14-2. They can be used as a reference sequence for vaccine quality control and surveillance of neurovirulence reversion following vaccination. Moreover, the present results further demonstrated the high genetic and phenotypic stabilities of the SA14-14-2 virus, suggesting the neurovirulence reversion of the vaccine strain will be highly unlikely.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Luciana Gomes Pedro Brandão, Guilherme Santoro-Lopes, Silas de Souza Oliveira, Edson Elias da Silva, Pedro Emmanuel Alvarenga Americano do Brasil Objectives To assess the prevalence of protective antibody titers to polioviruses in adults candidates for solid organ transplant (SOT), and to assess the immunogenic response to inactivated polio vaccine in this population. Methods The study included SOT candidates referred to Immunization Reference Centre of Evandro Chagas National Institute of Infectious Diseases from March 2013 to January 2016. It was conducted in 2 phases. The first one, a cross-sectional seroprevalence study, followed by an uncontrolled analysis of vaccine response among patients without protective antibody titers at baseline. Antibody titers to poliomyelitis were determined by microneutralization assay. Results Among 206 SOT candidates included, 156 (76%) had protective antibody titers to all poliovirus serotypes (95% CI: 70–81%). Proven history of oral vaccination in childhood was not associated with higher seroprevalence of protective antibody. In 97% of individuals without protective antibody titers at baseline, there was adequate vaccine response with one dose of inactivated polio vaccine. Conclusions A relevant proportion of adult candidates for SOT does not have protective titers of antibodies to one or more poliovirus serotype. One dose of inactivated vaccine elicited protective antibody titers in 97% of these subjects and should be routinely prescribed prior to SOT.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Louise Letley, Vanessa Rew, Rehana Ahmed, Katrine Bach Habersaat, Pauline Paterson, Tracey Chantler, Maria Saavedra-Campos, Robb Butler Introduction Due to regular vaccine preventable disease outbreaks and sub-optimal immunisation uptake in the London borough of Hackney, home to the largest Charedi Orthodox Jewish community in Europe, it was decided, in consultation with the community, to implement the WHO Tailoring Immunization Programmes approach (TIP). Design The WHO Tailoring Immunization Programmes (TIP) approach was used. TIP provides a framework based on behavioural insights methodology to identify populations susceptible to vaccine preventable diseases, diagnose supply and demand side barriers and enablers to vaccination and recommend evidence-informed responses to improve vaccination coverage. Results The results of the formative research and behavioural analysis challenged the assumption that a cultural or religious anti-vaccination sentiment existed within the community. Critical issues related to access to and convenience of immunisation services. Service providers in the area have challenges due to having to deliver immunisation services to the large numbers of children without additional resource. Where mothers were choosing to delay or refuse vaccinations their reasons were broadly similar to the wider population. The behavioural analysis identified potential categorisation of subgroups within the community enabling a more tailored approach to addressing concerns and meeting parents’ needs. Conclusion The TIP approach was an effective way of investigating factors linked to sub-optimal immunisation within the Charedi community. The use of behavioural insights enabled the categorisation of subgroups so that more targeted interventions could be developed. The comprehensive stakeholder engagement which is a key pillar of the TIP approach ensured a deeper understanding of the barriers and enablers to vaccination as well as increasing the level of ownership in the community. TIP should be considered as a useful approach to identify main facilitators and barriers to vaccination in communities with suboptimal immunisation uptake.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Gillian K. SteelFisher, Robert J. Blendon, Rustam Haydarov, William Lodge, Hannah Caporello, Sherine Guirguis, Saumya Anand, Julianne Birungi, Matthew R. Williams, Eran N. Ben-Porath, Denise O'Reilly, Christoph Sahm Background Using a survey conducted during the 2013–2014 polio outbreak in Somalia, this study examines attitudinal and knowledge-based threats to oral polio vaccine acceptance and commitment. Findings address a key gap, as most prior research focuses on endemic settings. Methods Between November 19 and December 21, 2013, we conducted interviews among 2003 caregivers of children under 5 years in select districts at high risk for polio transmission. Within each district, sample was drawn via a multi-stage cluster design with random route household selection. We calculated the percentage of caregivers who could not confirm recent vaccination and those uncommitted to future vaccination. We compared these percentages among caregivers with varying knowledge and attitudes, focusing on variables identified as threats in endemic settings, using controlled and uncontrolled comparisons. We also examined absolute levels of threat variables. Results Only 10% of caregivers could not confirm recent vaccination, but 32% were uncommitted to future vaccination. Being unvaccinated or uncommitted were related to multiple threat variables. For example, compared with relevant counterparts, caregivers were more likely to be unconfirmed and uncommitted if they did not trust vaccinators “a great deal” (unconfirmed: 9% vs. 2%; uncommitted: 49% vs. 28%), which is also true in endemic settings. Unlike endemic settings, symptom knowledge was related to commitment while rumor awareness was low and unrelated to past acceptance or commitment. Levels of trust and perceptions of OPV effectiveness were high, though perceptions of community support and awareness of logistics were lower. Conclusions As in endemic settings, outbreak responses will benefit from communications strategies focused on enhancing trust in vaccinators, institutions and the vaccine, alongside making community support visible. Disease facts may help motivate acceptance, and enhanced logistics information may help facilitate caregiver availability at the door. Quelling rumors early may be important to prevent them from becoming threats.