Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines

Kashiwagi, Yasuyo; Maeda, Mika; Kawashima, Hisashi; Nakayama, Tetsuo

doi:10.1016/j.vaccine.2014.04.018

Cited by 36 publications

(30 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been demonstrated that injection site reactogenicity is increased when the s.c. route is used versus the i.m. route (79). Because of this, we conducted additional vaccination studies aimed at determining the effectiveness of a NEAT domain cocktail when alum was the adjuvant and the vaccinations were administered i.m., the preferred human vaccination protocol.…”

Section: Resultsmentioning

confidence: 99%

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

et al. 2016

View full text Add to dashboard Cite

Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine.

show abstract

Section: Resultsmentioning

confidence: 99%

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Whilst studies have pertained to the presence of ABA inside APCs and cells of monocytic origin, none have shown the unequivocal presence of intracellular ABA612152129. A recent study has demonstrated the presence of in vivo injected aluminium adjuvant in rat at a muscular as opposed to a cellular level using lumogallion30. The direct identification of intracellular particulates of AlO(OH)-based adjuvants were therefore sought via the use of lumogallion as a sensitive molecular probe for aluminium2425.…”

Section: Discussionmentioning

confidence: 99%

Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line

Mold

Eriksson

Siesjö

et al. 2014

Sci Rep

View full text Add to dashboard Cite

Aluminium-based adjuvants (ABA) are the predominant adjuvants used in human vaccinations. While a consensus is yet to be reached on the aetiology of the biological activities of ABA several studies have identified shape, crystallinity and size as critical factors affecting their adjuvanticity. In spite of recent advances, the fate of ABA following their administration remains unclear. Few if any studies have demonstrated the unequivocal presence of intracellular ABA. Herein we demonstrate for the first time the unequivocal identification of ABA within a monocytic T helper 1 (THP-1) cell line, using lumogallion as a fluorescent molecular probe for aluminium. Use of these new methods revealed that particulate ABA was only found in the cell cytoplasm. Transmission electron microscopy revealed that ABA were contained within vesicle-like structures of approximately 0.5–1 μm in diameter.

show abstract

“…In our previous study, inflammatory nodules were detected at the injection sites of alum‐adjuvanted vaccines, DTaP, HPV (Cervarix and Gardasil), and PCV. However, vaccines without alum, Hib, JEV, and influenza virus vaccines did not provoke such a response . Cytokine profiles were investigated for 48 hr after vaccination with several vaccines in mouse models.…”

mentioning

confidence: 99%

Long‐term regulation of local cytokine production following immunization in mice

Nakayama

Kashiwagi

Kawashima

2018

Microbiology and Immunology

Self Cite

View full text Add to dashboard Cite

Vaccines based on pathogen components require adjuvants to enhance the antigen-specific adaptive immune response. Intramuscular injection of adjuvanted-vaccines induces inflammatory cytokines and inflammatory nodules at the injection site within 48 hr after injection (Vaccine 2014; 32: 3393-401). In the present study, long-term regulation of cytokine production was investigated at 3, 6, 24, and 48 hr, 5 and 7 days, and 2 and 4 weeks after immunization with human papilloma virus (HPV), diphtheria and tetanus toxoids combined with acellular pertussis (DTaP), Haemophilus influenza type B (Hib), and pneumococcal conjugated (PCV) vaccines in mouse models. The second dose was given 4 weeks later, and cytokine profiles were investigated 2, 5, and 7 days after re-immunization. IL-1β, IL-6, granulocyte-colony stimulating factor (G-CSF), and MCP-1 were produced from 3 hr and peaked at 48 hr after immunization with Cervarix in mice. IL-4, MCP-1, and TNF-α peaked at 5 or 7 days after immunization with Gardasil. These cytokines decreased 7 days after immunization with Cervarix and Gardasil. After the second dose, similar responses were observed. Both vaccines induced neutrophil extracellular traps (NET) in inflammatory nodules. The peak amount of IL-1β, IL-6, G-CSF, and MCP-1 was observed on day 5 of immunization and that of IL-4 on days 5-7 of immunization with DTaP, but no increase in IL-6 and G-CSF was observed after re-immunization. A similar response was noted after immunization with PCV13. An inflammatory response is essential for the development of adaptive immunity through the production of inflammatory cytokines.

show abstract

Inflammatory responses following intramuscular and subcutaneous immunization with aluminum-adjuvanted or non-adjuvanted vaccines

Cited by 36 publications

References 36 publications

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

Unequivocal identification of intracellular aluminium adjuvant in a monocytic THP-1 cell line

Long‐term regulation of local cytokine production following immunization in mice

Contact Info

Product

Resources

About