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): 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): Joyce H.S. You, Wai-kit Ming, Chak-fei Lee, Owen Tak-yin Tsang, Paul Kay-sheung Chan Background Adjuvanted herpes zoster (HZ) subunit vaccine is recommended for adults aged ≥50 years. This study aimed to investigate cost-effectiveness of HZ subunit vaccine for older adults at different age in Hong Kong. Methods A life-long Markov model was designed to simulate outcomes of four alternatives: Vaccination at model entry (age 50 years); deferring vaccination to 60 years; deferring vaccination to 70 years; and no vaccination. Outcome measures included direct cost, indirect cost, HZ and post-herpetic neuralgia incidences, quality-adjusted life years (QALYs) loss, and incremental cost per QALY saved (ICER). Model clinical inputs were derived from literature. HZ treatment costs were collected from a cohort of HZ patients (n = 218). One-way and probabilistic sensitivity analyses were performed. Results In base-case analysis, vaccination at 50 years showed highest QALYs saved and increment cost (0.00258; USD166), followed by deferring to 60 years (0.00215 QALYs saved; USD102) and deferring to 70 years (0.00134 QALYs; USD62) when comparing to no vaccination. ICERs of vaccination arms versus no vaccine (46,267–64,341 USD/QALY) were between 1–3 × gross domestic product (GPD) per capita in Hong Kong (USD43,530–USD130,590). One-way sensitivity analyses found vaccine cost to be the common and most influential parameter for ICER of each vaccination strategy to become 〈1 × GDP per capita. In probabilistic sensitivity analysis, vaccination at 50 years, deferring to 60 years and 70 years were accepted as cost-effective in 90% of time at willingness-to-pay (WTP) of 78,400 USD/QALY, 57,680 USD/QALY and 53,760 USD/QALY, respectively. Conclusions Cost-effectiveness of each strategy is highly subject to the vaccine cost and WTP threshold per QALY saved.

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): Al-Mamoon Badahdah, Harunor Rashid, Ameneh Khatami, Robert Booy Background Mass gatherings (MGs) such as the Hajj and Umrah pilgrimages are known to amplify the risk of invasive meningococcal disease (IMD) due to enhanced transmission of the organism between attendees. The burden of IMD at MGs other than Hajj and Umrah has not previously been quantified through a systematic review. Methods A systematic search for relevant articles in PubMed and Embase was conducted using MeSH terms; this was buttressed by hand searching. Following data abstraction, a narrative synthesis was conducted to quantify the burden of IMD at MGs and identify potential risk factors and mitigation measures. Results Thirteen studies reporting occurrence of IMD at MGs or similar crowded settings were identified. Eight studies reported cases or outbreaks in MGs of ≥1000 people; five others reported IMD in other crowded settings; all occurred between 1991 and 2015. All age groups were involved in the identified studies; however the majority of cases (∼80%) were young people aged 15–24 years. The number of affected people ranged from one to 321 cases and the overall crude estimate of incidence was calculated as 66 per 100,000 individuals. Serogroups A, C, B and W were identified, with serogroups A and C being most common. Of 450 cases of IMD reported in non-Hajj/Umrah MGs, 67 (14.9%) had fatal outcomes. Conclusion IMD outbreaks at non-Hajj/Umrah MGs are generally much smaller than Hajj-related outbreaks and affect mainly young people. Health education and vaccination should be considered for attendees of high risk non-Hajj/Umrah MGs, especially those involving adolescents and young adults.

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): Moran Ki, Hwa Young Choi, Minji Han, Jin-Kyoung Oh Background This prevalence-based, cost-of-illness study estimated the health care costs of human papillomavirus (HPV) infection-associated diseases in the era before the introduction of organized HPV vaccination for 12-year-old girls in 2016, South Korea. Methods The claims data provided by the National Health Insurance Service was used to estimate the prevalence of HPV-associated diseases and their direct medical costs, including costs related to hospitalizations, outpatient visits, and medications. Results A total of 1.3 million men and women used medical services for HPV-attributed diseases between 2002 and 2015. Among women, the most common diseases attributable to HPV were cervical dysplasia (64.4%), anogenital warts (12.9%), cervical carcinoma in situ (10.7%) and cervical cancer (2.6%), whereas anogenital warts (80.6%), benign neoplasms of larynx (14.3%), and anal cancers (8.9%) were most common among men. In 2015, the healthcare cost attributable to HPV was 124.9 million US dollars (USD) representing 69.0% of the annual cost of all HPV-associated diseases. At a cost of 75.1 million USD, cervical cancer contributed the largest economic burden in 2015 followed by cervical dysplasia (19.4 million USD) and cervical carcinoma in situ (10.7 million USD). These three conditions represented 58.2% of the total annual cost of all HPV-associated diseases, while 84.2% of the total annual cost was attributable to HPV. Annual health care costs increased from 42.6 million USD in 2002 to 180.9 million USD in 2015. Conclusion The healthcare costs associated with HPV-related diseases in Korea are substantial and increased between 2002 and 2015 mainly caused by increased number of patients. Expanding the target age for HPV vaccination of girls and introducing HPV vaccination for boys are possible ways of reducing the economic burden of HPV-associated disease and should be considered.

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): Anna Jarząb, Danuta Witkowska, Edmund Ziomek, Bartosz Setner, Aleksandra Czajkowska, Małgorzata Dorot, Zbigniew Szewczuk, Andrzej Gamian In earlier works we have described that mice immunized with outer membrane protein OmpC survive the challenge with live Shigella flexnerii 3a. We have also identified conformational epitope of this protein, that was recognized by mice antibodies. The aim of current work was to investigate whether synthetic OmpC epitope homologs can elicit immunological response sufficient in protecting mice against shigellosis. Several linear peptides containing RYDERY motif were synthesized and conjugated to poly-lysine. These conjugates appeared to be poor immunogens and to boost the immunological response an addition of the adjuvant (MPL) was required. Unfortunately, the MPL alone caused a very high immunological reaction that was masking response to peptidic epitope. Under those circumstances we used tetanus toxoid (TT) as the carrier protein for the peptides and the agent stimulating immunological response. Series of cyclic peptides, homologs of the OmpC main epitope were synthesized and conjugated to TT. The loop size in cyclic peptides varied by number of glycine residues, i.e., 1–3 residues added to the GLNRYDERYIGK motif. The linear GLNRYDERYIGC-TT was also prepared as the control. The latter conjugate gave the highest immunological response, followed by the cyclic-GGLNRYDERYIGC-TT and cyclic-GLNRYDERYIGC-TT. The third peptide, cyclic-GGGLNRYDERYIGC-TT, gave a very low response, although it was the most resistant to proteolysis. However, antibodies obtained against cyclic-GGLNRYDERYIGC-TT were more potent to recognize both OmpC and Shigella flexnerii 3a cells than the antibodies against linear GLNRYDERYIGC-TT. Furthermore, the monoclonal antibodies raised against linear GLNRYDERYIGC-TT showed 20-fold lower dissociation constant (KD) than the naturally occurring polyclonal antibodies from umbilical cord sera. Monoclonal antibodies also gave a weaker signal in electron microscope than mice and human polyclonal antibodies. In overall, our results point to cyclic peptides as better candidates for a vaccine development, since they are eliciting production of the higher affinity antibodies against Shigella cells and OmpC.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): M.S. Boukhvalova, A. Mbaye, S. Kovtun, K.C. Yim, T. Konstantinova, T. Getachew, S. Khurana, A.R. Falsey, J.C.G. Blanco Respiratory syncytial virus (RSV) is a significant cause of bronchiolitis and pneumonia. Protection against RSV is associated with neutralizing antibodies against the fusion (F) and attachment (G) glycoproteins. Several RSV vaccine candidates are in development, but their immunogenicity is hard to compare due to the little-understood differences between multiple RSV neutralizing antibody assays used. Existing assays utilize primarily Vero or HEp-2 cells, but their ability to detect G-neutralizing antibodies or antibodies against specific RSV strains is unclear. In this work, we developed an RSV microneutralization assay (MNA) using unmodified RSV and immortalized cell line derived from human airway epithelial cells (A549). Performance of A549-, HEp-2- and Vero-based MNA was compared under the same assay conditions (fixed amount of virus and cells) with regards to detection of neutralizing antibodies against RSV A or B viruses, G-reactive neutralizing antibodies, and effect of complement. Our results indicate that A549 cells yield the highest MNA titers, particularly in the RSV A/A2 MNA, are least susceptible to complement-enhancing effect of neutralizing titer readout and are superior to Vero or HEp-2 MNA at recognizing G-reactive neutralizing antibodies when no complement is used. Vero cells, however, can be more consistent at recognizing neutralizing antibodies against multiple RSV strains. The choice of substrate cells thus affects the outcome of MNA, as some immortalized cells better support detection of broader range of neutralizing antibodies, while others facilitate detection of G-targeting neutralizing antibodies, a long-thought prerogative of primary airway epithelial cells.