Viral vectors as vaccine platforms: from immunogenicity to impact

Ewer, Katie; Lambe, Teresa; Rollier, Christine S.; Spencer, Alexandra J.; Hill, Adrian V. S.; Dorrell, Lucy

doi:10.1016/j.coi.2016.05.014

Cited by 152 publications

(133 citation statements)

References 58 publications

(50 reference statements)

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“…Major advantages of using viral vectors as vaccine platform include their ability to infect broad range of host, to induce high levels of transgene expression and to stimulate both humoral and cellular immune responses (2, 3). Like their parental viruses, recombinant viral vectors contain pathogen-associated molecular patterns (PAMPs) to inherently stimulate innate immune responses, and therefore can confer intrinsic adjuvant effects to enhance vaccine-induced immunity (4).…”

Section: Introductionmentioning

confidence: 99%

Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16–STING–Type I IFN Pathway and AIM2 Sensor

Liu

Niu

Fan

et al. 2017

The Journal of Immunology

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Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about mechanisms underlying host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of antigen presenting cells (APCs) with two commonly used HIV vaccine vectors, ALVAC and Ad5, and herein reported identification of AIM2 as an innate sensor for ALVAC triggering strong inflammasome activation in both human and mouse APCs. Microarray and comprehensive gene knockout analyses (CRISPR/Cas9) identified that ALVAC stimulated the cGAS/IFI16-STING-Type I IFN pathway to prime AIM2, which was functionally required for ALVAC-induced inflammasome activation. We also provided evidence that different from ALVAC, Ad5 vector itself was unable to induce inflammasome activation, which was related to its inability to stimulate STING-Type I IFN pathway and to provide inflammasome priming signals. In pre-conditioned APCs, Ad5 vector could stimulate inflammasome activation through AIM2-independent mechanism. Therefore, our study identifies AIM2 inflammasome and cGAS/IFI16-STING-Type I IFN pathway as novel mechanism for host innate immunity to ALVAC vaccine vector.

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Section: Introductionmentioning

confidence: 99%

Priming and Activation of Inflammasome by Canarypox Virus Vector ALVAC via the cGAS/IFI16–STING–Type I IFN Pathway and AIM2 Sensor

Liu

Niu

Fan

et al. 2017

The Journal of Immunology

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“…Finally, this study relied on measures of humoral immunity, which may less reliably predict disease risk than measures of cell-mediated immunity [36][37][38]. However, serologic evidence of immunity is the international standard by which vaccine immunogenicity is currently measured [37][38][39][40][41], and although seronegativity and disease susceptibility are not identical, loss of detectible antibody is associated with an increased risk of breakthrough disease [42].…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection

Duncan

Witkop

Webber

et al. 2017

Vaccine

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seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection" (2017 a b s t r a c tBackground/Objectives: Infection with varicella zoster virus (VZV) produces lifelong immunity, but duration of post-vaccination immunity has not been established. The purpose of this study is to determine if a difference exists in the long-term seropositivity of anti-VZV antibodies in a cohort of young adults who were vaccinated against varicella as compared to a similar cohort with a history of chickenpox disease, and to determine which variables best predict waning seropositivity following varicella vaccination. Methods: This retrospective cohort study captures immunization and serology data from approximately 10,000 recruits who entered basic military training between January 1, 2008, and December 31, 2015, and who have childhood immunization records in the Air Force Aeromedical Services Information Management System. Varicella vaccine immunogenicity was determined relative to the immunogenicity of chickenpox disease, as measured by multiplex flow immunoassay. Among vaccine recipients, waning seroimmunity was modeled and adjusted for several important covariates. Results: Basic military trainees who received varicella vaccine in childhood were 24% less likely to be seropositive to VZV than trainees who were exempt from vaccine due to a history of chickenpox disease. There was no significant difference in seropositivity between male and female trainees. The odds of a vaccinated trainee being seropositive to VZV decreased by 8% with each year elapsed since vaccination. Seroprevalence declined below estimated herd immunity thresholds in vaccinated trainees born after 1994, and in the cohort as a whole for trainees born after 1995. Conclusion: Despite prior vaccination, seroimmunity in a large cohort of young adults unexposed to wildtype VZV failed to meet the estimated threshold for herd immunity. If vaccination in accordance with the current US VZV vaccination schedule is inadequate to maintain herd immunity, young adults not previously exposed to wild-type VZV may be at increased risk for varicella outbreaks.Published by Elsevier Ltd.

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“…They deliver HIV-1 antigens into host cells and stimulate immune responses. 116,117 A number of new vectors, including Ad26, Ad35, replication competent Ad4 and CMV vectors are currently being developed.…”

Section: New Vectorsmentioning

confidence: 99%