Organisms have evolved internal biological clocks to regulate their activities based on external environmental cues, such as light, temperature, and food. Environmental disruption of these rhythms, such as caused by constant light or frequent light schedule changes, has been shown to impair development, reduce survival, and increase infection susceptibility and disease progression in numerous organisms. However, the precise role of the biological clock in host-parasite interactions is understudied and has focused on unnatural host-parasite combinations in lab-adapted inbred models. Here, we use the natural interaction between monarch butterflies ( Danaus plexippus) and their virulent protozoan parasite, Ophryocystis elektroscirrha, to investigate the effects of constant light and frequent light schedule changes on development, survival, and parasite susceptibility. We show that constant light exposure slows the monarchs’ rate of development but does not increase susceptibility to parasitic infection. Furthermore, frequent schedule changes decrease parasite growth, but have no effect on egg-to-adult survival of infected monarchs. Interestingly, these conditions are usually disruptive to the biological clock, but do not significantly impact the clock of monarch larvae. These unexpected findings show that constant light and frequent schedule changes can uncouple host and parasite performance and highlight how natural relationships are needed to expand our understanding of clocks in host-parasite interactions.
Background Pediatric kidney transplant recipients (PKTR) are at risk of poor outcomes from COVID-19. Data on serologic responses to COVID-19 vaccines in PKTR remain sparse. We characterized the magnitude, breadth, and longevity of SARS-CoV-2 spike protein binding antibody responses in PKTR. Methods This single institution, prospective observational study enrolled PKTR presenting to a transplant clinic for routine care who had received or were eligible to receive a COVID-19 vaccine. Demographic data, history of prior COVID-19, and vaccination details were collected. Plasma samples obtained from standard-of-care residual specimens were analyzed for SARS-CoV-2 spike variant IgG using the MesoScale Discovery V-PLEX platform, which quantitatively measures antibodies to SARS-CoV-2 full-length spike wild-type (Wuhan-hu-1), Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529; BA.1) variants. Vaccine time points with > 5 samples available were analyzed. Geometric mean titers (GMTs) were calculated and log-transformed titers were compared using one-way ANOVA with Tukey’s post-hoc comparisons test. Results 61 PKTR enrolled (Table1); 47 (77%) received at least 1 dose of COVID-19 vaccine in transplant clinic. 47 (77%) PKTR had at least one sample available for analysis, but serial specimens were lacking for many. By 6 months post-dose 2 of COVID-19 mRNA vaccination, spike (Wuhan-hu-1) IgG titers had waned to pre-vaccination levels (GMT 24 vs 47 binding antibody units (BAU)/mL, P=0.988). Administration of a 3rd dose of mRNA vaccine significantly boosted IgG antibodies (GMT 492 BAU/mL, P=0.007), and titers were maintained at 3 months (GMT 656 BAU/mL, P=0.001) but gradually waned by 6 months (GMT 223 BAU/mL, P=0.070). Administration of a 4th dose elicited a non-significant increase in titers (GMT 905 BAU/mL, P=0.870). Binding IgG antibodies to SARS-CoV-2 variant spike proteins post-vaccination were not significantly different from Wuhan spike. Conclusion In this cohort of PKTR, a 3rd dose of COVID-19 mRNA vaccine significantly boosted broadly cross-reactive binding IgG antibodies to SARS-CoV-2 spike variants, including Omicron. Decreasing titers at 6 months post-dose 3 raise concern for waning protective immunity and support 4th dose vaccination. Disclosures Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc: Data Safety Monitoring Board|MedImmune: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Grant/Research Support|Micron: Grant/Research Support|NIH: Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines|PaxVax: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Data Adjudication and Data Safety Monitoring Boards|WCG and ACI Clinical: Data Adjudication Board Andi L. Shane, MD, MPH, MSc, International Scientific Association for Probiotics and Prebiotics (ISAPP): Honoraria Christina A. Rostad, MD, BioFire Inc, GSK, MedImmune, Micron, Merck, Novavax, PaxVax, Pfizer, Regeneron, Sanofi-Pasteur.: Grant/Research Support|Meissa Vaccines, Inc.: Co-inventor of RSV vaccine technology licensed to Meissa Vaccines, Inc.|NIH (Funding from NIH to conduct clinical trials of Moderna and Janssen COVID-19 vaccines): Grant/Research Support.
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