• Acute systemic DNA damage in youth does not impair immune defense with aging

      Pugh, Jason L.; Foster, Sarah A.; Sukhina, Alona S.; Petravic, Janka; Uhrlaub, Jennifer L.; Padilla-Torres, Jose; Hayashi, Tomonori; Nakachi, Kei; Smithey, Megan J.; Nikolich-Žugich, Janko; et al. (WILEY-BLACKWELL, 2016-08)
      Aging-related decline in immunity is believed to be the main driver behind decreased vaccine efficacy and reduced resistance to infections in older adults. Unrepaired DNA damage is known to precipitate cellular senescence, which was hypothesized to be the underlying cause of certain age-related phenotypes. Consistent with this, some hallmarks of immune aging were more prevalent in individuals exposed to whole-body irradiation (WBI), which leaves no anatomical repository of undamaged hematopoietic cells. To decisively test whether and to what extent WBI in youth will leave a mark on the immune system as it ages, we exposed young male C57BL/ 6 mice to sublethal WBI (0.5-4 Gy), mimicking human survivor exposure during nuclear catastrophe. We followed lymphocyte homeostasis thorough the lifespan, response to vaccination, and ability to resist lethal viral challenge in the old age. None of the irradiated groups showed significant differences compared with mock-irradiated (0 Gy) animals for the parameters measured. Even the mice that received the highest dose of sublethal WBI in youth (4 Gy) exhibited equilibrated lymphocyte homeostasis, robust T-and B-cell responses to live attenuated West Nile virus (WNV) vaccine and full survival following vaccination upon lethal WNV challenge. Therefore, a single dose of nonlethal WBI in youth, resulting in widespread DNA damage and repopulation stress in hematopoietic cells, leaves no significant trace of increased immune aging in a lethal vaccine challenge model.
    • Administering the HPV Vaccine to People Living with HIV: Providers' Perspectives

      Koskan, Alexis; Brennhofer, Stephanie A; Helitzer, Deborah; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth (SPRINGER, 2020-08)
      HIV-positive patients suffer disproportionate burden of anal cancer, a disease which is primarily caused by persistent infection with human papillomavirus (HPV) and is potentially preventable with the completion of the HPV vaccine series. Past research qualitatively explored HIV-positive patients' perspectives about the HPV vaccine. However, little is known about their healthcare practitioners' vaccine recommendation behaviors, the strongest influence on vaccine uptake. This study reports on in-depth interviews conducted with 25 healthcare practitioners who provide care for HIV-positive patients. Qualitative themes that emerged from the study included clinicians' HPV vaccination behaviors, HIV patient's willingness to get the HPV vaccine, the role of HIV-positive patients' immune functioning in terms of timing of HPV vaccine administration, and vaccinating HIV-positive patients over age 26. The majority of providers offered the vaccine at their healthcare facility. Participants varied in their opinions related to the importance of patients' CD4 count in terms of timing of HPV vaccine administration; some believed that patients' immune functioning should first be stabilized to receive the most benefit from the vaccine series. They also differed in the perceived benefit of offering the vaccine to patients over age 26. In light of the U.S. Food and Drug Administration's recent approval to extend HPV vaccination to adults up to age 45 years, more HIV-positive adults may benefit by receiving this vaccine series. Future efforts should ensure that providers regularly promote the HPV vaccine to their adult HIV-positive patients. Vaccinating HIV-positive patients may help reduce the burden of HPV-related cancers, particularly anal cancer.
    • A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment

      Milkman, Katherine L; Patel, Mitesh S; Gandhi, Linnea; Graci, Heather N; Gromet, Dena M; Ho, Hung; Kay, Joseph S; Lee, Timothy W; Akinola, Modupe; Beshears, John; et al. (National Academy of Sciences, 2021)
      Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment (N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19.