ArticlePloS one2016
TLR4 and TLR7/8 Adjuvant Combinations Generate Different Vaccine Antigen-Specific Immune Outcomes in Minipigs when Administered via the ID or IN Routes.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 32 citations in OpenAlex.
- Induction of innate cytokine responses by respiratory mucosal challenge with R848 in zebrafish, mice, and humans.The Journal of allergy and clinical immunology · 2019Trial
- A TRAC-478-adjuvanted recombinant N1 neuraminidase influenza virus vaccine induces balanced and broadly protective immune responses.NPJ vaccines · 2026Article
- Functional profiling of porcine precision-cut lymph node slices as anFrontiers in immunology · 2026Article
- mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation.Human vaccines & immunotherapeutics · 2025Review
- Pattern recognition receptors and their roles in antiviral innate immunity in livestock.Frontiers in immunology · 2025Review
- Nano-Assembled Polyphosphazene Delivery System Enables Effective Intranasal Immunization with Nipah Virus Subunit Vaccine.ACS applied bio materials · 2024Article
- Review
- The Use of an Adjuvant System Improves Innate and Adaptive Immune Response When Associated with aVaccines · 2023Article
- Article
- Evolution of Toll-like receptor 7/8 agonist therapeutics and their delivery approaches: From antiviral formulations to vaccine adjuvants.Advanced drug delivery reviews · 2021Review
- Formulation of Nanovaccines toward an Extended Immunity against Nicotine.ACS applied materials & interfaces · 2021Article
- 3M-052, a synthetic TLR-7/8 agonist, induces durable HIV-1 envelope-specific plasma cells and humoral immunity in nonhuman primates.Science immunology · 2020Article
- Mucosal Vaccine Approaches for Prevention of HIV and SIV Transmission.Current immunology reviews · 2019Article
- Immunomodulation as a Novel Strategy for Prevention and Treatment ofFrontiers in immunology · 2019Review
- Current challenges for cancer vaccine adjuvant development.Expert review of vaccines · 2018Review
- Rational incorporation of molecular adjuvants into a hybrid nanoparticle-based nicotine vaccine for immunotherapy against nicotine addiction.Biomaterials · 2018Article
- Virus-Like Particle, Liposome, and Polymeric Particle-Based Vaccines against HIV-1.Frontiers in immunology · 2018Review
- Adjuvant composition and delivery route shape immune response quality and protective efficacy of a recombinant vaccine forNPJ vaccines · 2018Article
- Strategies for Generating Diverse Antibody Repertoires Using Transgenic Animals Expressing Human Antibodies.Frontiers in immunology · 2018Article
- The synergistic effects of combining TLR ligand based adjuvants on the cytokine response are dependent upon p38/JNK signalling.Cytokine · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The induction of high levels of systemic and mucosal humoral immunity is a key goal for many prophylactic vaccines. However, adjuvant strategies developed in mice have often performed poorly in the clinic. Due to their closer similarity to humans, minipigs may provide a more accurate picture of adjuvant performance. Based on their complementary signalling pathways, we assessed humoral immune responses to model antigens after co-administration with the toll-like receptor 4 (TLR4) stimulator glucopyranosyl lipid adjuvant (GLA-AF) or the TLR7/8 agonist resiquimod (R848) (alone and in combination) via the intradermal (ID), intranasal (IN) or combined routes in the Gottingen minipig animal model. Surprisingly, we discovered that while GLA-AF additively enhanced the adjuvant effect of R848 when injected ID, it abrogated the adjuvant activity of R848 after IN inoculation. We then performed a route comparison study using a CN54 gp140 HIV Envelope model antigen adjuvanted with R848 + GLA-AF (ID) or R848 alone (IN). Animals receiving priming inoculations via one route were then boosted by the alternate route. Although differences were observed in the priming phase (IN or ID), responses converged upon boosting by the alternative route with no observable impact resultant from the order of administration (ID/IN vs IN/ID). Specific IgG responses were measured at a distal mucosal site (vaginal), although there was no evidence of mucosal linkage as these closely reflected serum antibody levels. These data indicate that the complex in vivo cross-talk between innate pathways are likely tissue specific and cannot be predicted by simple in vitro models.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.