Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Elizabeth P. Schlaudecker, Lilliam Ambroggio, Monica M. McNeal, Fred D. Finkelman, Sing Sing Way Background Influenza immunization is universally recommended during pregnancy to protect mothers and their offspring. However, pregnancy-induced shifts in vaccine responsiveness remain poorly defined. Methods Quantitative and qualitative shifts in the serological response to influenza vaccination were evaluated in healthy women throughout the course of pregnancy. Serum was obtained before and after vaccination among 71 pregnant and 67 non-pregnant women during the 2011–12 and 2012–13 influenza seasons. Serum hemagglutination inhibition (HAI) assay was used to investigate anti-influenza antibody responses by comparing pre-vaccine and post-vaccine geometric mean titers (GMTs) between groups for each antigen. IgG1, IgG2, IgG3, and IgG4 anti-influenza titers were also evaluated by enzyme-linked immunosorbent assay (ELISA). Pregnancy induced shifts in HAI titers and levels of each anti-influenza antibody isotype were evaluated using linear regression models. Results Post-vaccine GMTs at day 28 were significantly reduced for women vaccinated during pregnancy for A/California (H1N1) in 2011 ( p  = 0.027), A/Perth (H3N2) in 2011 ( p  = 0.037), and B/Wisconsin in 2012 ( p  = 0.039). Vaccine responses progressively declined with the initiation of vaccination later in pregnancy. Anti-H1N1 IgG1, IgG2, and IgG3 titers were reduced in pregnant women compared to non-pregnant controls, and these titers declined with pregnancy progression. The most striking differences were found for anti-H1N1 IgG1, where titers decreased by approximately 7% each week throughout pregnancy. Conclusions HAI responses elicited by immunization were significantly reduced during pregnancy for three different influenza vaccine antigens. Anti-H1N1 IgG1 was significantly lower in pregnant women and decreased throughout the course of pregnancy. Waning serological responsiveness to influenza vaccination with the progression of human pregnancy has important translational implications for when immunization should be optimally administered during pregnancy.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Qinying Yan, Zhigang Cheng, Houming Liu, Wanshui Shan, Zhide Cheng, Xuyong Dai, Yun Xue, Fan Chen Tuberculosis (TB) remains a major global public health problem. New immunization methods against TB are urgently needed. Plasmid DNA with a microneedle patch is a potentially attractive strategy to improve the immune effect. A DNA vaccine encoding the secreted protein Ag85B of Mycobacterium tuberculosis was immunized in the skin using microneedles, which can improve protective immunity compared to conventional intramuscular (IM) injection. There is no significant difference between microneedle patch (MNP) and IM immunization when the immunizing dose is low (4.2 μg). However, the results for detecting humoral immunity showed MNP immunization could better provoke an antibody response than IM when the dose is high (12.6 μg). A similar result was observed in cellular immune responses by measuring the cytokines in splenocytes. The effective protection of MNP can also be demonstrated by counting bacteria and analyzing the survival rate. This study indicated that DNA vaccination in the skin using dissolving microneedles may provide a new strategy against TB.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Angela K. Shen, Rob Warnock, Steve Chu, Jeffrey A. Kelman Annual influenza vaccination campaigns emphasize the importance of getting vaccinated against influenza. These campaigns offer potential opportunities to raise awareness of all vaccines. We explored the peak timing of the receipt of influenza and other routinely recommended vaccinations. We examined administrative claims data of 31 million Medicare fee-for-service beneficiaries, eligible to receive vaccinations administered from 2013 to 2015 from Medicare Part B (medical insurance) and Medicare Part D (prescription drug benefit). From 2013 to 2015, 88% of over 50 million influenza vaccination claims occurred in September, October, and November. Claims for pneumococcal (42%), herpes zoster (36%), and tetanus-containing (32%) vaccines were also concentrated during these months. For pneumococcal vaccines, this concentration occurred across various provider settings, including traditional doctor’s offices, pharmacies, and hospitals. Herpes zoster (92%) and tetanus-containing (72%) vaccines were largely administered in the pharmacy. Annual influenza vaccination efforts offer additional opportunities to assess, recommend, and administer other recommended vaccinations.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Petra Zimmermann, Nigel Curtis There is substantial variation between individuals in the immune response to vaccinations. The intestinal microbiome plays a crucial rule in the development and regulation of the immune system and therefore its composition might affect how individuals respond to vaccinations. In this review, we summarise studies that investigated the influence of the intestinal microbiome on humoral and cellular vaccine responses. To date, only four studies (three in infants and one in adults) have investigated the influence of the intestinal microbiome on vaccine responses. All found an association between the intestinal microbiome and vaccine responses. Despite the heterogeneity in study designs (including different vaccines, schedules, timing of collection of stool and blood samples, analysis methods and reporting of results on different taxonomic levels), findings across studies were consistent: a higher relative abundance of the phylum Actinobacteria (oral and parenteral vaccines) and Firmicutes (oral vaccines) was associated with both higher humoral and higher cellular vaccine responses, while a higher relative abundance of the phylum Proteobacteria (oral and parenteral vaccines) and Bacteroidetes (oral vaccines) was associated with lower responses. Further, well-designed, adequately powered studies using whole-genome sequencing (to include the influence of viruses, fungi and parasites) are needed to investigate in more detail the influence of the intestinal microbiome on vaccine responses. This will help identify strategies to improve vaccine efficacy and duration of protection, particularly in infancy when the intestinal microbiome is more amenable to external influences and plays an important role in the development of the immune system.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Marija Vujadinovic, Selina Khan, Koen Oosterhuis, Taco G. Uil, Kerstin Wunderlich, Sarra Damman, Satish Boedhoe, Annemiek Verwilligen, Jonathan Knibbe, Jan Serroyen, Hanneke Schuitemaker, Roland Zahn, Gert Scheper, Jerome Custers, Jort Vellinga Oncogenic high-risk human papillomavirus (HPV) infections cause a substantial number of genital and non-genital cancers worldwide. Approximately 70% of all cervical cancers are caused by the high-risk HPV16 and 18 types. The remaining 30% can be attributed to twelve other high-risk HPV-types. Highly efficacious 2-valent, 4-valent and 9-valent L1 protein based prophylactic HPV vaccines are available however with limited cross-protection. To further increase the coverage, development of a multivalent cross-protective HPV vaccine is currently focused on the conserved N-terminus of HPV’s L2 protein. We have developed a vaccine candidate based on the rare human adenovirus type 35 (HAdV35) vector that displays a concatemer of L2 protein epitopes from four different HPV-types via protein IX (pIX). A mix of two heterologous HAdV35 pIX-L2 display vectors present highly conserved linear epitopes of nine HPV-types. Each HAdV35 pIX-L2 display vector exhibits a good manufacturability profile. HAdV35 pIX-L2 display vaccine vectors were immunogenic and induced neutralizing antibodies against HPV-types included in the vaccine and cross-neutralizing antibodies against distant a HPV-type not included in the vaccine in mice. The HAdV35 pIX-L2 display vectors offer an opportunity for a multivalent HAdV-based prophylactic HPV vaccine.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Jiansong Zhang, Meifen Wang, Nini Zhou, Yijuan Shen, Yufeng Li The Gram-negative pathogen toxigenic P. multocida causes progressive atrophic rhinitis (PAR) in swine throughout the world. Although some vaccines are being developed against PAR, their efficacy has not been evaluated using carbopol. In our study, a mixture of killed B. bronchiseptica and P. multocida bacteria, combined with recombinant proteins containing the C- and N-termini of PMT, was emulsified using two different adjuvants (ISA-15A and carbopol 971). The efficacy of these two vaccines was evaluated in a mouse model. Balb/C mice were immunized twice at a 14-day interval. Two weeks after the secondary immunization, blood samples were collected and the mice were challenged with toxigenic P. multocida . Thirty-five days later, the mice were euthanized, blood and tissue samples were collected. Compared with mice inoculated with vaccine emulsified with ISA-15A, higher titers of SN (1:64) and significantly increased levels of TNF-α, IL-6 and IL-17A were observed in mice inoculated with vaccine emulsified with the carbopol 971P. Especially, mice immunized with vaccine emulsified with the carbopol 971P had no detectable pathological changes in snouts or organs after challenge . The results demonstrated that carbopol adjuvanted vaccine provides good protection against PAR and P. multocida infection which can induce robust humoral and cell-mediated responses. We conclude that the carbopol adjuvanted vaccine is a good candidate for PAR prevention.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Yves Fougère, Samir El Houss, Joan-Carles Suris, Sylvie Rouvenaz-Defago, Damien Miletto, Lucie Von der Weid, Fanny Willen, Joanne Anesta Williams-Smith, Mario Gehri, Pierre Alex Crisinel Background Worldwide coverage of hepatitis B (HB) vaccination is increasing. This should be considered when determining the best strategy for catch-up HB vaccination in migrant children, who rarely have written proof of past immunizations. This study aimed to estimate HB vaccine protection, chronic HB prevalence and to identify determinants of vaccine protection. Methods Newly arrived migrant children at Lausanne University Hospital from October 2014 to July 2017 were prospectively enrolled. Children and adolescents aged 1–18 years were approached for inclusion if they had no proof of past vaccinations and accepted a single dose of injected HB vaccine. HB surface antibody (anti-HBs) serology was performed after 4–6 weeks. Anti-HBs ≥100 IU/L were considered consistent with a booster-type antibody response. Patients with anti-HBs 〈100 IU/L received additional dose(s) of HB vaccine, after exclusion of chronic HB in children with anti-HBs 〈10 IU/L. Potential determinants of vaccine response were compared between children with and without booster-type response. Results Two hundred children were available for analysis. Median age was 8.9 years (IQR 4.8–12.9), and 97 (49%) were female. The majority (n = 124, 62%) came from the region classified by the WHO as eastern Mediterranean. One hundred and sixty-one children (81%) had a booster-type antibody response. Only 1 patient (〈1%) had chronic HB. In the multivariate analysis, younger age (OR per decreasing-year, 1.28; 95%CI, 1.05–1.57; p = 0.017) and migration from an urban area (OR 1.16; 95%CI, 1.01–1.33; p = 0.043) were the only significant determinants of booster-type response. Conclusion Post-vaccine serology may be used to identify a high proportion of individuals in our pediatric migrant population with previous immunization for HB. Our study also showed extremely low prevalence of chronic HB. No variable could definitively determine the results of serology. Post-vaccine serology represents the most effective strategy in this context of high vaccine coverage.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Aaron S. Wallace, Kong Krey, John Hustedt, Eleanor Burnett, Narin Choun, Danni Daniels, Margaret L. Watkins, Sann Chan Soeung, Richard Duncan Introduction Missed opportunities for vaccination (MOV) can result in inadequate protection against disease. Although healthcare provider reluctance to open multi-dose, lyophilized vaccine vials (particularly the measles-containing vaccine [MCV]) for every eligible child due to concerns about wasting vaccine is a known reason for MOV, little is known about providers’ related attitudes and practices. Methods In 100 randomly selected health facilities and 24 districts of Cambodia, we surveyed healthcare providers and their district supervisors regarding routine vaccine administration and wastage knowledge and practices, and child caregivers (five per facility) regarding MOV. Vaccine stock management data covering six months were reviewed to calculate facility and district level wastage rates and vaccine usage patterns for six vaccines, including a recently introduced second dose of MCV (MCV2). Results Response rates were 100/100 (100%) among facility staff, 48/48 (100%) among district staff, and 436/500 (87%) among caregivers. Mean facility-level wastage rates varied from 4% for single-dose diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine to 60% for 10-dose MCV; district-level wastage rates for all vaccines were 0%. Some vaccines had lower wastage rates in large facilities compared to small facilities. The mean MCV wastage rate was the same before and immediately after MCV2 introduction. Providers reported waiting for a mean of two children prior to opening an MCV vial, and 71% of providers reported offering MCV vaccination less frequently during scheduled vaccination sessions than other vaccines. Less than 5% of caregivers reported that their child had been turned away for vaccination, most frequently (65%) for MCV. Discussion Although the MCV wastage rate in our study was in line with national targets, providers reported waiting for more than one child before opening an MCV vial, contrary to vaccine management guidelines. Future research should explore the causal links between provider practices related to vaccine wastage and their impact on vaccination coverage.

Description: Publication date: 16 July 2018 Source: Vaccine, Volume 36, Issue 30 Author(s): Akihiko Saitoh, Nobuhiko Okabe The Japanese immunization program has made considerable recent progress. The introduction of several new vaccines, especially foreign-produced vaccines, and the inclusion of important new vaccines in the National Immunization Program (NIP) are closing the “vaccine gap”, i.e., the delay in the Japanese immunization program relative to programs in other developed countries. Major progress in the Japanese immunization program since 2014 includes (1) elimination of measles in March 2015, (2) introduction of a varicella vaccine as a routine immunization in the NIP in October 2015, and (3) introduction of hepatitis B virus vaccines as routine immunizations in the NIP in October 2016. Despite these promising developments, important issues remain. First, the government withdrew the active recommendation for human papilloma virus vaccines temporarily in 2013. The withdrawal has continued and unresolved despite new scientific evidence confirming the safety of these vaccines. Second, a few important voluntary vaccines, including vaccines for mumps and rotavirus, have not been included in the NIP since their introduction to Japan. Finally, there are concerns related to a shortage of mandatory domestic vaccines, which was caused by a natural disaster in the area where a vaccine-producing factory was located. Additionally, the manufacturer included unauthorized additives in some vaccine products with falsifying the production-process records. To avoid problems related to vaccine shortages, essential vaccines need to be stockpiled, and the future vaccine needs for children should to be discussed. New initiatives must continue to close the vaccine gap, as this will protect children living in Japan from vaccine-preventable diseases.