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Abstract An influenza vaccine approach that overcomes the problem of viral sequence diversity and provides long-lived heterosubtypic protection is urgently needed to protect against pandemic influenza viruses. Here, to determine if lung-resident effector memory T cells induced by cytomegalovirus (CMV)-vectored vaccines expressing conserved internal influenza antigens could protect against lethal influenza challenge, we immunize Mauritian cynomolgus macaques (MCM) with cynomolgus CMV (CyCMV) vaccines expressing H1N1 1918 influenza M1, NP, and PB1 antigens (CyCMV/Flu), and challenge with heterologous, aerosolized avian H5N1 influenza. All six unvaccinated MCM died by seven days post infection with acute respiratory distress, while 54.5% (6/11) CyCMV/Flu-vaccinated MCM survived. Survival correlates with the magnitude of lung-resident influenza-specific CD4 + T cells prior to challenge. These data demonstrate that CD4 + T cells targeting conserved internal influenza proteins can protect against highly pathogenic heterologous influenza challenge and support further exploration of effector memory T cell-based vaccines for universal influenza vaccine development.

Summary: Highly pathogenic avian influenza A H5N1 viruses cause high mortality in humans and have pandemic potential. Effective vaccines and treatments against this threat are urgently needed. Here, we have refined our previously established model of lethal H5N1 infection in cynomolgus macaques. An inhaled aerosol virus dose of 5.1 log10 plaque-forming unit (pfu) induced a strong febrile response and acute respiratory disease, with four out of six macaques succumbing after challenge. Vaccination with three doses of adjuvanted seasonal quadrivalent influenza vaccine elicited low but detectable neutralizing antibody to H5N1. All six vaccinated macaques survived four times the 50% lethal dose of aerosolized H5N1, while four of six unvaccinated controls succumbed to disease. Although vaccination did not protect against severe influenza, vaccinees had reduced respiratory dysfunction and lower viral load in airways compared to controls. We anticipate that our macaque model will play a vital role in evaluating vaccines and antivirals against influenza pandemics.

Introduction: Paid family leave (PFL) has the potential to reduce persistent health disparities. This study aims to characterize differences in access to paid leave by industry sector and occupational class. Methods: The Bay Area Parental Leave Survey of Mothers included respondents 18 years of age or older who worked in the San Francisco Bay Area and gave birth from 2016 to 2017. Using linear probability models, we examined differences in five separate measures of PFL by industry sector and occupational class. We extended our regression analysis to simulate the full pay equivalent (FPE) weeks of leave that would have been taken under hypothetical scenarios of increased uptake and wage replacement rates. Results: Our study included 806 women in private for-profit or non-profit jobs. In fully adjusted models, blue-collar workers were 10.9% less likely to take 12 weeks of paid parental leave versus white-collar workers (95% CI: -25.9, 4.1). Respondents were 19.2% less likely receive 100% of their regular pay if they worked in education and health services (−29.1, −9.3) and 17.0% less likely if they worked in leisure and hospitality (−29.5, −4.4) versus respondents in professional and financial services. Respondents in leisure and hospitality reported 1.6 fewer FPE weeks of leave versus respondents in professional and financial services (−2.73, −0.42) and blue-collar respondents reported an average of 1.5 fewer FPE weeks versus white-collar workers (−2.66, −0.42). In our simulation analysis, when we manipulated rates of uptake for paid leave, the disparities in FPE by industry sector and occupational class were eliminated. Conclusion: We observed substantial inequities in access to paid leave by industry sector and occupational class. These findings underscore the potential importance of universal PFL programs with universal benefits to reduce clear inequities that persist within the labor market today.