Single-cycle adenovirus vectors in the current vaccine landscape

Barry, Michael A.

doi:10.1080/14760584.2018.1419067

Cited by 26 publications

(30 citation statements)

References 102 publications

(120 reference statements)

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“…In contrast, an E1 intact replication-competent Ad (RC-Ad) delivers one copy, but then replicates the antigen gene DNA 10,000-fold to amplify antigen production and immune responses [14-25]. Although RC-Ads are consistently reported to be substantially more potent than RD-Ads, RC-Ads actually risk causing adenovirus infections in patients (reviewed in [26]).…”

Section: Resultsmentioning

confidence: 99%

Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses

Matchett

Anguiano-Zarate

Barry

2018

Glob Vaccines Immunol

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HIV-1 infections occur during sexual contact at mucosal surfaces. Vaccines need to provide mucosal barrier protection and stimulate systemic immune responses to control HIV spread. Most vaccines are delivered by systemic immunization via intramuscular (IM) injection route. While this can drive systemic and mucosal immune responses, there are data show that mucosal immunization may be superior at driving responses at mucosal barriers. To explore this question, we immunized mice with replicating single-cycle adenovirus (SC Ad) vaccines expressing clade B HIV-1 envelope (Env) by intramuscular (IM), intranasal (IN), or intravaginal (IVAG) routes to compare vaccine responses. SC-Ads generated significant antibodies against Env after only a single immunization by the IN route, but not the other routes. These animals were boosted by the same route or by the mucosal IVAG routes. IM and IN primed animals generated strong antibody responses regardless of the boosting route. In contrast, IVAG primed animals failed to generate robust antibodies whether they were boosted by the IVAG or IM routes. These data suggest there may be benefits in first educating the immune system at mucosal sites during HIV vaccination. IN and IM prime-boost were then compared in Syrian hamsters which support SC-Ad DNA replication. In this case, IN immunization again was the only route that generated significant Env antibodies after a single immunization. Following a boost by IN or IM routes, IN primed animals had significantly higher antibody responses than the IM primed animals. Env antibodies could still be detected one year after immunization, but only in animals that received at least one mucosal IN immunization. These data suggest that there is merit in vaccination by mucosal routes.

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Section: Resultsmentioning

confidence: 99%

Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses

Matchett

Anguiano-Zarate

Barry

2018

Glob Vaccines Immunol

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“…However, the tradeoff for enhanced immunogenicity is the concern for potential reversion of the attenuated viral vector to virulence, especially when using a replication-competent vector (18). Replication-defective and single-cycle viral vectors are attractive alternatives that have an increased safety profile and, in some cases, are still able to elicit a strong immune response (19,20). More details about the known viral vectors and their recent advances in vaccine development will be discussed in our forthcoming review article (Vrba, S.M., et al, in preparation).…”

Section: Introductionmentioning

confidence: 99%

Emerging Concepts and Technologies in Vaccine Development

et al. 2020

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Despite the success of vaccination to greatly mitigate or eliminate threat of diseases caused by pathogens, there are still known diseases and emerging pathogens for which the development of successful vaccines against them is inherently difficult. In addition, vaccine development for people with compromised immunity and other pre-existing medical conditions has remained a major challenge. Besides the traditional inactivated or live attenuated, virus-vectored and subunit vaccines, emerging non-viral vaccine technologies, such as viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer innovative approaches to address existing challenges of vaccine development. They have also significantly advanced our understanding of vaccine immunology and can guide future vaccine development for many diseases, including rapidly emerging infectious diseases, such as COVID-19, and diseases that have not traditionally been addressed by vaccination, such as cancers and substance abuse. This review provides an integrative discussion of new non-viral vaccine development technologies and their use to address the most fundamental and ongoing challenges of vaccine development.

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“…SC-Ads generate antibodies and T cells responses that increase over 12 months after single immunization vs. HIV, influenza, Ebola, Zika, or C. difficile antigens [38,[41][42][43][44][45][46][47][48]. SC-Ad carrying influenza hemagglutinin (HA) produced markedly more antigen than RD-Ad in vitro, requiring 33- While RC-Ads are documented to be more potent than RD-Ad vectors, replication-competent Ads pose a real risk of causing adenovirus infections as a side-effect of vaccination.…”

Section: Introductionmentioning

confidence: 99%

Genetic Adjuvants in Replicating Single-Cycle Adenovirus Vectors Amplify Systemic and Mucosal Immune Responses against HIV-1 Envelope

et al. 2020

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Most infections occur at mucosal surfaces. Providing a barrier of protection at these surfaces may be a useful strategy to combat the earliest events in infection when there are relatively few pathogens to address. The majority of vaccines are delivered systemically by the intramuscular (IM) route. While IM vaccination can drive mucosal immune responses, mucosal immunization at intranasal (IN) or oral sites can lead to better immune responses at mucosal sites of viral entry. In macaques, IN immunization with replicating single-cycle adenovirus (SC-Ads) and protein boosts generated favorable mucosal immune responses. However, there was an apparent "distance effect" in generating mucosal immune responses. IN immunization generated antibodies against HIV envelope (env) nearby in the saliva, but weaker responses in samples collected from the distant vaginal samples. To improve on this, we tested here if SC-Ads expressing genetic adjuvants could be used to amplify antibody responses in distant vaginal samples when they are codelivered with SC-Ads expressing clade C HIV env immunogen. SC-Ads env 1157 was coadministered with SC-Ads expressing 4-1BBL, granulocyte macrophage colony-stimulating factor (GMCSF), IL-21, or Clostridoides difficile (C. diff.) toxin fragments by IN or IM routes. These data show that vaginal antibody responses were markedly amplified after a single immunization by the IN or IM routes, with SC-Ad expressing HIV env if this vaccine is complemented with SC-Ads expressing genetic adjuvants. Furthermore, the site and combination of adjuvants appear to "tune" these antibody responses towards an IgA or IgG isotype bias. Boosting these priming SC-Ad responses with another SC-Ad or with SOSIP native-like env proteins markedly amplifies env antibody levels in vaginal washes. Together, this data may be useful in informing the choice of route of delivery adenovirus and peptide vaccines against HIV-1.

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Single-cycle adenovirus vectors in the current vaccine landscape

Cited by 26 publications

References 102 publications

Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses

Comparison of systemic and mucosal immunization with replicating Single cycle Adenoviruses

Emerging Concepts and Technologies in Vaccine Development

Genetic Adjuvants in Replicating Single-Cycle Adenovirus Vectors Amplify Systemic and Mucosal Immune Responses against HIV-1 Envelope

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