The intersection of sex, gender, and aging on influenza and COVID-19 vaccine outcomes

The influenza and COVID-19 vaccines are essential public health tools for older adults, who are vulnerable to severe disease following infection. For both diseases, although sex and gender are known to influence epidemiologic outcomes, their role in the context of vaccination is largely unexplored. The three aims of this dissertation each address how sex or gender differences can be leveraged to successfully vaccinate older adults against viral respiratory diseases. First, in data collected from a longitudinal cohort of older adults (≥ 75 years of age) who repeatedly received the high-dose trivalent inactivated influenza vaccine, pre-vaccination titers predicted vaccine responses. Turning to pre-vaccination titers as an outcome of importance, an interaction between age and sex emerged. Titers to two influenza strains decreased with age in males but not in females, suggesting that older females mount more durable responses to vaccination than older males. Second, using the same cohort of older adults, we measured humoral responses induced by three doses of a SARS-CoV-2 mRNA vaccine. Age and frailty were associated with reduced antibody responses in males, but not females, suggesting that older males may be vulnerable to breakthrough infections following two doses. The third vaccine dose restored functional antibody responses, eliminated disparities caused by sex, age, and frailty, and boosted responses to variants of concern, highlighting the importance of third dose coverage in older adults, especially males. Finally, turning to the role of gender in vaccine behavior, we performed in-depth interviews to understand how older adults made the decision to receive the COVID-19 vaccine, and how intersections between gender and race shaped this process. While some participants eagerly accepted vaccination, others had significant hesitations due perceived risks associated with the vaccine product and infrastructure, which varied by gender and race. Most ultimately accepted vaccination due to fear of COVID-19, with additional motivators depending on lived experiences of gender and race. Taken together, these data support a central role for sex and gender in vaccine outcomes for older adults and more tailored approaches to vaccinology. By harnessing the heterogeneity in vaccine outcomes, we can better serve this vulnerable population

Seroprevalence of rubella antibodies and determinants of susceptibility to rubella in a cohort of pregnant women in Canada, 2008–2011

Long term control of rubella and congenital rubella syndrome relies on high population-level immunity against rubella, particularly among women of childbearing age. In Canada, all pregnant women should be screened so that susceptible new mothers can be offered vaccination for rubella before discharge. This study was undertaken to estimate rubella susceptibility in a cohort of pregnant women in Canada and to identify associated socio-economic and demographic factors. Biobanked plasma samples were obtained from the Maternal-Infant Research on Environmental Chemicals (MIREC) study, in which pregnant women were recruited between 2008 and 2011. Socio-demographic characteristics and obstetric histories were collected. Second trimester plasma samples (n = 1,752) were tested for rubella-specific IgG using an in-house enzyme-linked immunosorbent assay. The percentage of women with IgG titers <5 IU/mL, 5–10 IU/mL, and 10 IU/mL were 2.3%, 10.1%, and 87.6%, respectively. Rates of seronegativity, defined as <5 IU/mL, were 3.1% in women who had no previous live birth and 1.6% in women who had given birth previously. Among the latter group, seronegativity was higher in women with high school education or less (adjusted OR (aOR) 5.93, 95% CI 2.08–16.96) or with a college or trade school diploma (aOR 3.82, 95% CI 1.45–10.12), compared to university graduates, and those born outside Canada (aOR 2.60, 95% CI 1.07–6.31). In conclusion, a large majority of pregnant women were found to be immune to rubella. Further research is needed to understand inequalities in vaccine uptake or access, and more effort is needed to promote catch-up measles-mumps-rubella vaccination among socioeconomically disadvantaged and immigrant women of childbearing age

Three doses of COVID-19 mRNA vaccine induce class-switched antibody responses in inflammatory arthritis patients on immunomodulatory therapies

Patients with inflammatory arthritis (IA) are at increased risk of severe COVID-19 due to medication-induced immunosuppression that impairs host defenses. The aim of this study was to assess antibody and B cell responses to COVID-19 mRNA vaccination in IA patients receiving immunomodulatory therapies. Adults with IA were enrolled through the Johns Hopkins Arthritis Center and compared with healthy controls (HC). Paired plasma and peripheral blood mononuclear cell (PBMC) samples were collected prior to and 30 days or 6 months following the first two doses of mRNA vaccines (D2; HC=77 and IA=31 patients), or 30 days following a third dose of mRNA vaccines (D3; HC=11 and IA=96 patients). Neutralizing antibody titers, total binding antibody titers, and B cell responses to vaccine and Omicron variants were analyzed. Anti-Spike (S) IgG and S-specific B cells developed appropriately in most IA patients following D3, with reduced responses to Omicron variants, and negligible effects of medication type or drug withholding. Neutralizing antibody responses were lower compared to healthy controls after both D2 and D3, with a small number of individuals demonstrating persistently undetectable neutralizing antibody levels. Most IA patients respond as well to mRNA COVID-19 vaccines as immunocompetent individuals by the third dose, with no evidence of improved responses following medication withholding. These data suggest that IA-associated immune impairment may not hinder immunity to COVID-19 mRNA vaccines in most individuals

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements