Intranasal Immunization of Mice with Influenza Vaccine in Combination with the Adjuvant LT-R72 Induces Potent Mucosal and Serum Immunity Which Is Stronger than That with Traditional Intramuscular Immunization

Barackman, J. D.; Ott, Gary; O’Hagan, Derek T.

doi:10.1128/iai.67.8.4276-4279.1999

Cited by 58 publications

(13 citation statements)

References 29 publications

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“…The pandemic influenza H1N1 virus in 2009 spread to approximately 214 countries and regions and caused at least 18,449 deaths (http://www.who.int/csr/don). As the primary method for protecting against these diseases up-to-date, vaccination via intramuscular or subcutaneous injection plays an outstanding role in evoking systemic immune responses, but it is not sufficient to induce mucosal antibodies, which are of great importance for the prevention of respiratory infectious diseases (1). More suitable and effective vaccination strategies are in urgent need to overcome this problem.…”

Section: Introductionmentioning

confidence: 99%

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Zheng

Zhang

et al. 2014

Pharm Res

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Section: Introductionmentioning

confidence: 99%

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Zheng

Zhang

et al. 2014

Pharm Res

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“…4). It has been www.nature.com/scientificreports/ previously reported that BALB/c mice respond to the influenza vaccine with a T helper type 2 (Th2) response, indicating a higher stimulation of IgG1, known to neutralize the viral particles [46][47][48] . However, the mixed squalene adjuvant had a lower IgG1:IgG2a ratio suggesting either a slightly lower or higher stimulation of IgG1 or IgG2a, respectively, as compared to the other groups.…”

Section: Discussionmentioning

confidence: 99%

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Tateno

Stone

Srodulski

et al. 2020

Sci Rep

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The triterpene oil squalene is an essential component of nanoemulsion vaccine adjuvants. It is most notably in the MF59 adjuvant, a component in some seasonal influenza vaccines, in stockpiled, emulsion-based adjuvanted pandemic influenza vaccines, and with demonstrated efficacy for vaccines to other pandemic viruses, such as SARS-CoV-2. Squalene has historically been harvested from shark liver oil, which is undesirable for a variety of reasons. In this study, we have demonstrated the use of a Synthetic Biology (yeast) production platform to generate squalene and novel triterpene oils, all of which are equally as efficacious as vaccine adjuvants based on physiochemical properties and immunomodulating activities in a mouse model. These Synthetic Biology adjuvants also elicited similar IgG1, IgG2a, and total IgG levels compared to marine and commercial controls when formulated with common quadrivalent influenza antigens. Injection site morphology and serum cytokine levels did not suggest any reactogenic effects of the yeast-derived squalene or novel triterpenes, suggesting their safety in adjuvant formulations. These results support the advantages of yeast produced triterpene oils to include completely controlled growth conditions, just-in-time and scalable production, and the capacity to produce novel triterpenes beyond squalene.

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“…Thus, although these LT mutants induce potent antigen‐specific mucosal and systemic humoral responses when administered with other protein antigens (e.g. influenza HA 26 ), they are poor inducers of humoral responses following mucosal immunizations with HIV gag protein. Therefore, the ability of the LT mutant adjuvants to induce immunity against coadministered proteins may be antigen dependent.…”

Section: Discussionmentioning

confidence: 99%

Genetically detoxified mutants of heat‐labile enterotoxin from Escherichia coli are effective adjuvants for induction of cytotoxic T‐cell responses against HIV‐1 gag‐p55

Neidleman¹,

Vajdy²,

Ugozzoli³

et al. 2000

Immunology

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There is an urgent need for prophylactic and therapeutic vaccines against human immunodeficiency virus (HIV). Mucosal immunization strategies have great potential to elicit both mucosal and systemic cellular immunity required to protect against HIV-induced acquired immune deficiency syndrome (AIDS). However, mucosal immunizations with soluble protein antigens generally require adjuvants. In this study, we tested two mutants of the heat-labile enterotoxin (LT) from Escherichia coli, LTK63: with no measurable ADP-ribosyltransferase activity, and LTR72: with residual ADP-ribosyltransferase activity, as mucosal adjuvants for induction of cytotoxic T lymphocyte (CTL) responses to coadministered HIV gag p55 protein. We found that intranasal (i.n.) immunizations with HIV gag p55 protein coadministered with LTK63 or LTR72 induced systemic CTL responses comparable to that obtained following intramuscular (i. m.) immunizations with the same adjuvants. Moreover, oral coadministration of LTR72, but not LTK63, resulted in local as well as systemic p55-specific CTL responses in mesenteric lymph nodes (MLN) and spleens (SP) of the immunized mice. These data have important implications for current efforts to develop a safe vaccine against HIV.

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Intranasal Immunization of Mice with Influenza Vaccine in Combination with the Adjuvant LT-R72 Induces Potent Mucosal and Serum Immunity Which Is Stronger than That with Traditional Intramuscular Immunization

Cited by 58 publications

References 29 publications

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration

Synthetic Biology-derived triterpenes as efficacious immunomodulating adjuvants

Genetically detoxified mutants of heat‐labile enterotoxin from Escherichia coli are effective adjuvants for induction of cytotoxic T‐cell responses against HIV‐1 gag‐p55

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