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Vaccines, Volume 1, Issue 3 (September 2013), Pages 204-397

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Research

Jump to: Review, Other

Open AccessCommunication Post Approval Human Papillomavirus Vaccine Uptake Is Higher in Minorities Compared to Whites in Girls Presenting for Well-Child Care
Vaccines 2013, 1(3), 250-261; doi:10.3390/vaccines1030250
Received: 29 May 2013 / Revised: 8 June 2013 / Accepted: 11 July 2013 / Published: 17 July 2013
Cited by 1 | PDF Full-text (523 KB) | HTML Full-text | XML Full-text
Abstract
Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes
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Since introduction of the human papillomavirus (HPV) vaccine, there remains low uptake compared to other adolescent vaccines. There is limited information postapproval about parental attitudes and barriers when presenting for routine care. This study evaluates HPV vaccine uptake and assesses demographics and attitudes correlating with vaccination for girls aged 11–12 years. A prospective cohort study was performed utilizing the University of Virginia (UVA) Clinical Data Repository (CDR). The CDR was used to identify girls aged 11–12 presenting to any UVA practice for a well-child visit between May 2008 and April 2009. Billing data were searched to determine rates of HPV vaccine uptake. The parents of all identified girls were contacted four to seven months after the visit to complete a telephone questionnaire including insurance information, child’s vaccination status, HPV vaccine attitudes, and demographics. Five hundred and fifty girls were identified, 48.2% of whom received at least one HPV vaccine dose. White race and private insurance were negatively associated with HPV vaccine initiation (RR 0.72, 95% CI 0.61–0.85 and RR 0.85, 95% CI 0.72–1.01, respectively). In the follow-up questionnaire, 242 interviews were conducted and included in the final cohort. In the sample, 183 (75.6%) parents reported white race, 38 (15.7%) black race, and 27 (11.2%) reported other race. Overall 85% of parents understood that the HPV vaccine was recommended and 58.9% of parents believed the HPV vaccine was safe. In multivariate logistic regression, patients of black and other minority races were 4.9 and 4.2 times more likely to receive the HPV vaccine compared to their white counterparts. Safety concerns were the strongest barrier to vaccination. To conclude, HPV vaccine uptake was higher among minority girls and girls with public insurance in this cohort. Full article
(This article belongs to the Special Issue Confidence in Vaccines)
Open AccessArticle Enhanced Efficacy of a Codon-Optimized DNA Vaccine Encoding the Glycoprotein Precursor Gene of Lassa Virus in a Guinea Pig Disease Model When Delivered by Dermal Electroporation
Vaccines 2013, 1(3), 262-277; doi:10.3390/vaccines1030262
Received: 31 May 2013 / Revised: 8 July 2013 / Accepted: 10 July 2013 / Published: 18 July 2013
Cited by 4 | PDF Full-text (512 KB) | HTML Full-text | XML Full-text
Abstract
Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC) that expressed the LASV glycoprotein precursor gene (GPC). This
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Lassa virus (LASV) causes a severe, often fatal, hemorrhagic fever endemic to West Africa. Presently, there are no FDA-licensed medical countermeasures for this disease. In a pilot study, we constructed a DNA vaccine (pLASV-GPC) that expressed the LASV glycoprotein precursor gene (GPC). This plasmid was used to vaccinate guinea pigs (GPs) using intramuscular electroporation as the delivery platform. Vaccinated GPs were protected from lethal infection (5/6) with LASV compared to the controls. However, vaccinated GPs experienced transient viremia after challenge, although lower than the mock-vaccinated controls. In a follow-on study, we developed a new device that allowed for both the vaccine and electroporation pulse to be delivered to the dermis. We also codon-optimized the GPC sequence of the vaccine to enhance expression in GPs. Together, these innovations resulted in enhanced efficacy of the vaccine. Unlike the pilot study where neutralizing titers were not detected until after virus challenge, modest neutralizing titers were detected in guinea pigs before challenge, with escalating titers detected after challenge. The vaccinated GPs were never ill and were not viremic at any timepoint. The combination of the codon-optimized vaccine and dermal electroporation delivery is a worthy candidate for further development. Full article
(This article belongs to the Special Issue DNA Vaccines)
Open AccessCommunication A Multidisciplinary Research Agenda for Understanding Vaccine-Related Decisions
Vaccines 2013, 1(3), 293-304; doi:10.3390/vaccines1030293
Received: 9 June 2013 / Revised: 21 June 2013 / Accepted: 2 July 2013 / Published: 18 July 2013
Cited by 7 | PDF Full-text (346 KB) | HTML Full-text | XML Full-text
Abstract
There is increasingly broad global recognition of the need to better understand determinants of vaccine acceptance. Fifteen social science, communication, health, and medical professionals (the “Motors of Trust in Vaccination” (MOTIV) think tank) explored factors relating to vaccination decision-making as a step to
[...] Read more.
There is increasingly broad global recognition of the need to better understand determinants of vaccine acceptance. Fifteen social science, communication, health, and medical professionals (the “Motors of Trust in Vaccination” (MOTIV) think tank) explored factors relating to vaccination decision-making as a step to building a multidisciplinary research agenda. One hundred and forty seven factors impacting decisions made by consumers, professionals, and policy makers on vaccine acceptance, delay, or refusal were identified and grouped into three major categories: cognition and decision-making; groups and social norms; and communication and engagement. These factors should help frame a multidisciplinary research agenda to build an evidence base on the determinants of vaccine acceptance to inform the development of interventions and vaccination policies. Full article
(This article belongs to the Special Issue Confidence in Vaccines)
Open AccessArticle Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques
Vaccines 2013, 1(3), 305-327; doi:10.3390/vaccines1030305
Received: 16 May 2013 / Revised: 5 July 2013 / Accepted: 10 July 2013 / Published: 19 July 2013
Cited by 5 | PDF Full-text (724 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies
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HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. Full article
(This article belongs to the Special Issue DNA Vaccines)
Open AccessArticle An HIV Vaccine for South-East Asia—Opportunities and Challenges
Vaccines 2013, 1(3), 348-366; doi:10.3390/vaccines1030348
Received: 3 June 2013 / Revised: 25 July 2013 / Accepted: 5 August 2013 / Published: 14 August 2013
Cited by 2 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China
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Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China with a growing number of circulating recombinant forms due to increasing human contact, particularly in large urban centers, tourist locations and in sites of common infrastructure. A vaccine countering CRF01_AE is a priority for the region. An Asia HIV vaccine against expanding B/E or BCE recombinant forms should be actively pursued. A major challenge that remains is the conduct of efficacy trials in heterosexual populations in this region. Men who have sex with men represent the main target population for future efficacy trials in Asia. Coupling HIV vaccines with other prevention modalities in efficacy trials might also be envisaged. These new avenues will only be made possible through the conduct of large-scale efficacy trials, interdisciplinary teams, international collaborations, and strong political and community commitments. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessArticle Enhanced Delivery and Potency of Self-Amplifying mRNA Vaccines by Electroporation in Situ
Vaccines 2013, 1(3), 367-383; doi:10.3390/vaccines1030367
Received: 26 June 2013 / Revised: 12 August 2013 / Accepted: 14 August 2013 / Published: 22 August 2013
Cited by 6 | PDF Full-text (1824 KB) | HTML Full-text | XML Full-text
Abstract
Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and
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Nucleic acid-based vaccines such as viral vectors, plasmid DNA (pDNA), and mRNA are being developed as a means to address limitations of both live-attenuated and subunit vaccines. DNA vaccines have been shown to be potent in a wide variety of animal species and several products are now licensed for commercial veterinary but not human use. Electroporation delivery technologies have been shown to improve the generation of T and B cell responses from synthetic DNA vaccines in many animal species and now in humans. However, parallel RNA approaches have lagged due to potential issues of potency and production. Many of the obstacles to mRNA vaccine development have recently been addressed, resulting in a revival in the use of non-amplifying and self-amplifying mRNA for vaccine and gene therapy applications. In this paper, we explore the utility of EP for the in vivo delivery of large, self-amplifying mRNA, as measured by reporter gene expression and immunogenicity of genes encoding HIV envelope protein. These studies demonstrated that EP delivery of self-amplifying mRNA elicited strong and broad immune responses in mice, which were comparable to those induced by EP delivery of pDNA. Full article
(This article belongs to the Special Issue DNA Vaccines)
Open AccessArticle Elucidating the Kinetics of Expression and Immune Cell Infiltration Resulting from Plasmid Gene Delivery Enhanced by Surface Dermal Electroporation
Vaccines 2013, 1(3), 384-397; doi:10.3390/vaccines1030384
Received: 16 July 2013 / Revised: 13 August 2013 / Accepted: 21 August 2013 / Published: 28 August 2013
Cited by 7 | PDF Full-text (837 KB) | HTML Full-text | XML Full-text
Abstract
The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future
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The skin is an attractive tissue for vaccination in a clinical setting due to the accessibility of the target, the ease of monitoring and most importantly the immune competent nature of the dermal tissue. While skin electroporation offers an exciting and novel future methodology for the delivery of DNA vaccines in the clinic, little is known about the actual mechanism of the approach and the elucidation of the resulting immune responses. To further understand the mechanism of this platform, the expression kinetics and localization of a reporter plasmid delivered via a surface dermal electroporation (SEP) device as well as the effect that this treatment would have on the resident immune cells in that tissue was investigated. Initially a time course (day 0 to day 21) of enhanced gene delivery with electroporation (EP) was performed to observe the localization of green fluorescent protein (GFP) expression and the kinetics of its appearance as well as clearance. Using gross imaging, GFP expression was not detected on the surface of the skin until 8 h post treatment. However, histological analysis by fluorescent microscopy revealed GFP positive cells as early as 1 h after plasmid delivery and electroporation. Peak GFP expression was observed at 24 h and the expression was maintained in skin for up to seven days. Using an antibody specific for a keratinocyte cell surface marker, reporter gene positive keratinocytes in the epidermis were identified. H&E staining of treated skin sections demonstrated an influx of monocytes and granulocytes at the EP site starting at 4 h and persisting up to day 14 post treatment. Immunological staining revealed a significant migration of lymphocytic cells to the EP site, congregating around cells expressing the delivered antigen. In conclusion, this study provides insights into the expression kinetics following EP enhanced DNA delivery targeting the dermal space. These findings may have implications in the future to design efficient DNA vaccination strategies for the clinic. Full article
(This article belongs to the Special Issue DNA Vaccines)

Review

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Open AccessReview Sustaining Vaccine Confidence in the 21st Century
Vaccines 2013, 1(3), 204-224; doi:10.3390/vaccines1030204
Received: 4 March 2013 / Revised: 17 May 2013 / Accepted: 27 May 2013 / Published: 24 June 2013
Cited by 7 | PDF Full-text (629 KB) | HTML Full-text | XML Full-text
Abstract
Vaccination provides many health and economic benefits to individuals and society, and public support for immunization programs is generally high. However, the benefits of vaccines are often not fully valued when public discussions on vaccine safety, quality or efficacy arise, and the spread
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Vaccination provides many health and economic benefits to individuals and society, and public support for immunization programs is generally high. However, the benefits of vaccines are often not fully valued when public discussions on vaccine safety, quality or efficacy arise, and the spread of misinformation via the internet and other media has the potential to undermine immunization programs. Factors associated with improved public confidence in vaccines include evidence-based decision-making procedures and recommendations, controlled processes for licensing and monitoring vaccine safety and effectiveness and disease surveillance. Community engagement with appropriate communication approaches for each audience is a key factor in building trust in vaccines. Vaccine safety/quality issues should be handled rapidly and transparently by informing and involving those most affected and those concerned with public health in effective ways. Openness and transparency in the exchange of information between industry and other stakeholders is also important. To maximize the safety of vaccines, and thus sustain trust in vaccines, partnerships are needed between public health sector stakeholders. Vaccine confidence can be improved through collaborations that ensure high vaccine uptake rates and that inform the public and other stakeholders of the benefits of vaccines and how vaccine safety is constantly assessed, assured and communicated. Full article
(This article belongs to the Special Issue Confidence in Vaccines)
Open AccessReview Vector Design for Improved DNA Vaccine Efficacy, Safety and Production
Vaccines 2013, 1(3), 225-249; doi:10.3390/vaccines1030225
Received: 14 May 2013 / Revised: 12 June 2013 / Accepted: 18 June 2013 / Published: 25 June 2013
Cited by 10 | PDF Full-text (653 KB) | HTML Full-text | XML Full-text
Abstract
DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through
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DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy. Full article
(This article belongs to the Special Issue DNA Vaccines)
Figures

Open AccessReview Innate Immune Signaling by, and Genetic Adjuvants for DNA Vaccination
Vaccines 2013, 1(3), 278-292; doi:10.3390/vaccines1030278
Received: 13 June 2013 / Revised: 6 July 2013 / Accepted: 9 July 2013 / Published: 18 July 2013
Cited by 10 | PDF Full-text (685 KB) | HTML Full-text | XML Full-text
Abstract
DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans,
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DNA vaccines can induce both humoral and cellular immune responses. Although some DNA vaccines are already licensed for infectious diseases in animals, they are not licensed for human use because the risk and benefit of DNA vaccines is still controversial. Indeed, in humans, the immunogenicity of DNA vaccines is lower than that of other traditional vaccines. To develop the use of DNA vaccines in the clinic, various approaches are in progress to enhance or improve the immunogenicity of DNA vaccines. Recent studies have shown that immunogenicity of DNA vaccines are regulated by innate immune responses via plasmid DNA recognition through the STING-TBK1 signaling cascade. Similarly, molecules that act as dsDNA sensors that activate innate immune responses through STING-TBK1 have been identified and used as genetic adjuvants to enhance DNA vaccine immunogenicity in mouse models. However, the mechanisms that induce innate immune responses by DNA vaccines are still unclear. In this review, we will discuss innate immune signaling upon DNA vaccination and genetic adjuvants of innate immune signaling molecules. Full article
(This article belongs to the Special Issue DNA Vaccines)
Open AccessReview Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection
Vaccines 2013, 1(3), 328-342; doi:10.3390/vaccines1030328
Received: 5 June 2013 / Revised: 11 July 2013 / Accepted: 23 July 2013 / Published: 9 August 2013
PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+
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The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection. Full article
(This article belongs to the Special Issue HIV Vaccines)

Other

Jump to: Research, Review

Open AccessOpinion Trust in Vaccines: Why It Takes More than Good Faith
Vaccines 2013, 1(3), 343-347; doi:10.3390/vaccines1030343
Received: 29 May 2013 / Revised: 21 June 2013 / Accepted: 10 July 2013 / Published: 12 August 2013
Cited by 2 | PDF Full-text (218 KB) | HTML Full-text | XML Full-text
Abstract
This Vaccines issue on “Confidence in Vaccines” provides sound evidence through multiple perspectives of life-saving impacts when vaccination programs are effectively implemented in a population. Yet there remain challenges to achieving this impact, including scientific, medical, manufacturing, policy-related and logistical issues. Additionally, socio-cultural,
[...] Read more.
This Vaccines issue on “Confidence in Vaccines” provides sound evidence through multiple perspectives of life-saving impacts when vaccination programs are effectively implemented in a population. Yet there remain challenges to achieving this impact, including scientific, medical, manufacturing, policy-related and logistical issues. Additionally, socio-cultural, religious and political agendas can come into play, taking public health hostage and sometimes allowing the circulation of myths regarding vaccination. All of these challenges play a role in public confidence in vaccines and vaccination. What we trust, we embrace. What we do not trust, we do not embrace. Full article
(This article belongs to the Special Issue Confidence in Vaccines)

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