Browsing by Subject "Immune responses"

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    Lack of immune response after mRNA vaccination to SARS‐CoV‐2 in a solid organ transplant patient
    (Wiley, 2021-09) Rusk, Debra S.; Strachan, Christian C.; Hunter, Benton R.; Emergency Medicine, School of Medicine
    The recent approval and distribution of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have been a major development in the fight against the current coronavirus disease 2019 (COVID‐19) pandemic. The first two vaccines approved in the United States, mRNA‐1273, and BNT162b2, are both messenger RNA (mRNA) based and highly effective in immunocompetent persons, but efficacy in patients on immunosuppressants has not been established. Additionally, data suggests these patients are less likely than immunocompetent people to develop neutralizing antibodies after COVID‐19 infection. Given the high risk of poor outcomes in organ transplant and immunosuppressed patients, effective vaccination is paramount in this group. We present the first reported case of a solid organ transplant patient who failed to achieve seroconversion after two doses of mRNA vaccine. This case has significant implications about how immunosuppressed patients should be counseled about SARS‐CoV‐2 vaccination and the protection provided. Physicians should remain clinically suspicious for infection with SARS‐CoV‐2 despite vaccination status in solid organ transplant patients.
  • Thumbnail Image
    Item
    PAFR activation of NF-κB p65 or p105 precursor dictates pro- and anti-inflammatory responses during TLR activation in murine macrophages
    (SpringerNature, 2016-08-24) Ishizuka, Edson K.; Filgueiras, Luciano Ribeiro; Rios, Francisco J.; Serezani, Carlos H.; Jancar, Sonia; Department of Microbiology and Immunology, IU School of Medicine
    Platelet-activating factor receptor (PAFR) is a G protein-coupled receptor (GPCR) implicated in many diseases. Toll-like receptors (TLRs) play a critical role in shaping innate and adaptive immune responses. In this study, we investigated whether PAFR signaling changes the macrophages responsiveness to agonists of TLR2 (Pam3Cys), TLR4 (LPS), and TLR3 agonist Poly(I:C). Exogenous PAF inhibited the production of pro-inflammatory cytokines (IL-12p40, IL-6, and TNF-α) and increased anti-inflammatory IL-10 in macrophages challenged with Pam3Cys and LPS, but not with Poly (I:C). PAF did not affect mRNA expression of MyD88, suggesting that PAF acts downstream the adaptor. PAF inhibited LPS-induced phosphorylation of NF-κB p65 and increased NF-κB p105 phosphorylation, which is processed in the proteasome to generate p50 subunit. The PAF potentiation of IL-10 production was dependent on proteasome processing but independent of NF-κB transactivation domain. Inhibition of p50 abolished the PAF-induced IL-10 production. These findings indicate that the impaired transcriptional activity of the p65 subunit and the enhanced p105 phosphorylation induced by PAF are responsible for down regulation of pro-inflammatory cytokines and up regulation of IL-10, respectively, in LPS-challenged macrophages. Together, our data unveil a heretofore unrecognized role for PAFR in modulating activation of NF-κB in macrophages
  • Thumbnail Image
    Item
    Persistence of Anti-SARS-CoV-2 Spike IgG Antibodies Following COVID-19 Vaccines
    (Dove Press, 2022-07-29) Alharbi, Naif Khalaf; Al-Tawfiq, Jaffar A.; Alwehaibe, Amal; Alenazi, Mohamed W.; Almasoud, Abdulrahman; Algaisi, Abdullah; Alhumaydhi, Fahad A.; Hashem, Anwar M.; Bosaeed, Mohammed; Alsagaby, Suliman A.; Medicine, School of Medicine
    Purpose: This study was conducted to investigate antibody immune responses induced by BNT162b2 and AZD1222 human COVID-19 vaccines in Riyadh city, Saudi Arabia. Patients and methods: ELISA was used to evaluate antibodies, against the SARS-CoV-2 spike S1 protein, in serum samples from 432 vaccinated individuals at six time points: pre-vaccination (baseline), post-prime, post-boost, 6-months, and 1 year post-vaccination, and 3 weeks post a third dose. Virus microneutralization assay was used to confirm antibody responses in a subset of samples. Results: Anti-SARS-CoV-2 spike IgG were detected in most subjects post-prime, reached a peak level post-boost, and remained at high level at the 6-month follow-up. At 1 year post-vaccine, the antibody levels were low but increased to a significant level higher than the peak following a third dose. The third dose was given at an average of 250 days after the second dose. The virus microneutralization assay confirmed the neutralization activity of the induced SARS-CoV-2 IgG antibodies. The vaccines induced higher IgG titres at post-prime (p=0.0001) and 6 months (p=0.006) in previously infected individuals. An increased interval between prime and boost, more than recommended time, appeared to enhance the IgG levels (p=0004). Moreover, the vaccines induced higher IgG levels in younger subjects (p=0.01). Conclusion: These data provide insights and build on the current understanding of immune responses induced by these two vaccines; and support a third boosting dose for these COVID-19 vaccines.