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): Marco Grasse, Andreas Meryk, Carina Miggitsch, Beatrix Grubeck-Loebenstein Multivalent tetanus and diphtheria toxoid containing vaccines belong to the most frequently applied vaccines. However, there is an imbalance in the degree of protection against the two antigens with insufficient long-term protection against diphtheria, particularly in the elderly population. We have previously reported a positive correlation between granulocyte macrophage-colony stimulating factor (GM-CSF) and the production of diphtheria-specific antibodies. Therefore, in the present study we analyzed the effects of in vivo applied recombinant GM-CSF on immunization with multivalent tetanus/diphtheria vaccine in mice of different age. In vivo application of GM-CSF lead to enhanced production of diphtheria-specific antibodies as well as more diphtheria-specific CD4 + T cells following vaccination with multivalent tetanus/diphtheria vaccine. In contrast, the humoral and cellular immune response to the tetanus component was unaltered. Furthermore, application of GM-CSF resulted in more splenic CD11b + dendritic cells (DCs) with a higher MHC-II expression. GM-CSF also induced a stronger recruitment of CD11b + DCs to the injected muscle. Most remarkably, GM-CSF was able to boost the diphtheria-specific immune response to the multivalent vaccine in aged mice. This study demonstrates that local administration of GM-CSF is able to improve immune responsiveness to the diphtheria component of multivalent tetanus/diphtheria vaccine in young and old mice. This information could be useful for the future design of vaccines for the elderly.

Description: Publication date: 25 July 2018 Source: Vaccine, Volume 36, Issue 31 Author(s): Pravesh D. Kara, Arshad S. Mather, Alri Pretorius, Thireshni Chetty, Shawn Babiuk, David B. Wallace Lumpy skin disease virus (LSDV) is responsible for causing severe economic losses to cattle farmers throughout Africa, the Middle East, and more recently, South-Eastern Europe and Russia. It belongs to the Capripoxvirus genus of the Poxviridae family, with closely related sheeppox and goatpox viruses. Like other poxviruses, the viral genome codes for a number of genes with putative immunomodulatory capabilities. Current vaccines for protecting cattle against lumpy skin disease (LSD) based on live-attenuated strains of field isolates passaged by cell culture, resulting in random mutations. Although generally effective, these vaccines can have drawbacks, including injection site reactions and/or limited immunogenicity. A pilot study was conducted using a more targeted approach where two putative immunomodulatory genes were deleted separately from the genome of a virulent LSDV field isolate. These were open reading frame (ORF) 005 and ORF008, coding for homologues of an interleukin 10-like and interferon-gamma receptor-like gene, respectively. The resulting knockout constructs were evaluated in cattle for safety, immunogenicity and protection. Severe post-vaccinal reactions and febrile responses were observed for both constructs. Two calves inoculated with the ORF008 knockout construct developed multiple lesions and were euthanised. Following challenge, none of the animals inoculated with the knockout constructs showed any external clinical signs of LSD, compared to the negative controls. Improved cellular and humoral immune responses were recorded in both of these groups compared to the positive control. The results indicate that at the high inoculation doses used, the degree of attenuation achieved was insufficient for further use in cattle due to the adverse reactions observed.

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: 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): 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): Rebecca C. Brady, Lisa A. Jackson, Sharon E. Frey, Andi L. Shane, Emmanuel B. Walter, Geeta K. Swamy, Elizabeth P. Schlaudecker, Elena Szefer, Mark Wolff, Monica Malone McNeal, David I. Bernstein, Mark C. Steinhoff Background Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are both licensed for administration to nursing mothers. Little is known about the potential for transmission of LAIV viruses from the mother to the infant and the comparative breast milk antibody responses to LAIV and IIV. Methods We performed a randomized, double-blind study comparing the immunogenicity of LAIV to IIV when administered to nursing mothers. The safety of LAIV to IIV in women and their infants was also compared. Women received LAIV + intramuscular placebo, or IIV + intranasal placebo on Day 0. Breast milk and nasal swabs (from women and infants) were collected on Days 0, 2, and 8 for detection of LAIV. Breast milk and serum antibody responses were measured at Days 0 and 28. The primary hypothesis was that LAIV would provide superior induction of breast milk IgA responses to influenza as compared to IIV when administered to nursing mothers. Results Breast milk IgG, breast milk IgA (H1N1 only), serum hemagglutination inhibition (HAI), and serum IgG responses were significantly higher following administration of IIV compared to LAIV. Receipt of either LAIV or IIV was safe in women and their infants. One (1%) LAIV recipient transmitted vaccine virus to her infant who remained well. No influenza virus was detected in breast milk. Conclusions Breast milk and serum antibody responses were higher for IIV compared to LAIV. LAIV and IIV were safe for nursing women but there was one (1%) possible transmission of LAIV to an infant. This study suggests that IIV may be the preferred vaccine for nursing mothers.

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): Walter H.B. Demczuk, Irene Martin, Shalini Desai, Averil Griffith, Laurence Caron-Poulin, Brigitte Lefebvre, Allison McGeer, Gregory J. Tyrrell, George G. Zhanel, Jonathan Gubbay, Linda Hoang, Paul N. Levett, Paul Van Caeseele, Rita Raafat Gad, David Haldane, George Zahariadis, Gregory German, Jennifer Daley Bernier, Lori Strudwick, Michael R. Mulvey The 13-valent conjugate vaccine (PCV13) was recommended for childhood immunization programs in 2010 in Canada and has decreased the incidence of invasive pneumococcal disease (IPD) in children and changed the epidemiology of IPD in adults. This study investigated the epidemiology of IPD in adults 65 years of age and older in Canada. A total of 7282 invasive S. pneumoniae isolated from adults ≥65 years old were serotyped from 2010 to 2016 and antimicrobial susceptibility was performed on 2527 isolates. Serotyping was performed by Quellung reaction using commercial antisera and antimicrobial susceptibilities were determined by broth microdilution. PCV7 serotypes decreased non-significantly from 2010 to 2016 from 9.1% (n = 96) to 6.7% (n = 72) while the additional six PCV13 serotypes declined significantly from 39.5% (n = 418) to 18.6% (n = 201) (p 〈 0.05). The 23-valent pneumococcal polysaccharide vaccine (PPV23) and non-vaccine (NVT) serotypes increased from 26.3% (n = 278) to 36.2% (n = 393) (p 〈 0.05), and from 25.1% (n = 266) to 38.4% (n = 416) (p 〈 0.05), respectively. There were no significant changes in antimicrobial resistance rates from 2011 to 2016: 24.1% of the IPD from adults ≥65 years were resistant to clarithromycin (n = 609), 10.0% to doxycycline (n = 254), 11.8% to penicillin (n = 299), 5.2% to cefuroxime (n = 131), 6.6% to clindamycin (n = 168), 6.0% to trimethoprim-sulfamethoxazole (n = 152), and 0.5% (n = 12) to ceftriaxone. Although overall incidence of IPD in adults ≥65 years has remained relatively constant from 2010 to 2016, childhood PCV13 vaccination programs have been successful in indirectly reducing IPD caused by PCV13 serotypes in adults through herd immunity effects.

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.