Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the human upper respiratory tract, is less well known. Here, we enumerate and phenotype T cells in nasal mucosa and blood using flow cytometry before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n = 21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ increase in number ~12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p = 0.058 and p = 0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decrease post-vaccination. Similar increases in nasal CD8+CD69+CD103− T cells are observed, particularly following the second dose. CD4+ cells co-expressing CCR6 and CD161 are also increased in abundance following both doses. Stimulation of nasal CD8+ T cells with SARS-CoV-2 spike peptides elevates expression of CD107a at 2- and 6-months (p = 0.0096) post second vaccine dose, with a subset of donors also expressing increased cytokines. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.
Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FOXP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded ~12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103- T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.
Regulatory T cells (Tregs) play important roles in tissue homeostasis, but few studies have investigated tissue Tregs in the context of genital inflammation, HIV target cell density, and vaginal microbiota in humans. In women from Nairobi (n=64), the proportion of CD4+ CD25+ CD127low Tregs in the endocervix correlated with those in blood (r=0.31, p=0.01), with a higher Treg frequency observed in the endocervix (median 3.8 vs 2.0%, p<0.0001). Most Tregs expressed FoxP3 in both compartments, and CTLA-4 expression was higher on endocervical Tregs compared to blood (median 50.8 vs 6.0%, p<0.0001). More than half (34/62, 55%) of participants displayed a non-Lactobacillus dominant vaginal microbiota, which was not associated with endocervical Tregs or CD4+ T cell abundance. In a multivariable linear regression, endocervical Treg proportions were inversely associated with the number of elevated pro-inflammatory cytokines (p=0.03). Inverse Treg associations were also observed for specific cytokines including IL-1β, G-CSF, Eotaxin, IL-1RA, IL-8, and MIP-1 β. Higher endocervical Treg proportions were associated with lower abundance of endocervical CD4+ T cells (0.30 log10 CD4+ T cells per log10 Treg, p=0.00028), with a similar trend for Th17 cells (p=0.09). Selectively increasing endocervical Tregs may represent a pathway to reduce genital tract inflammation in women.
Background Among certain communities and nations, the sexual health rights of women living with HIV (WLHIV) are often neglected and considered less important. Social, cultural, and religious believes may restrict safer sexual practices. This study examines the sexual health knowledge, attitude, and practices of WLHIV in Banten Province, Indonesia, and the factors influencing these practices. Methods A cross-sectional written survey of 209 WLHIV aged 18 to 50 years from seven Banten Province regions, was conducted between May and November 2017 using five peer recruiters. Descriptive and binary regression analysis were performed. Results The majority were Muslim (87.6%), married (58.9%), and high-school graduated (88.6%). 31.4% experienced intimate partner violence (IPV). 77% had some knowledge of sexually transmitted infection (STI), sourcing information from health care providers (56.9%) and the internet (23.0%). Most believed that a woman could refuse sexual intercourse with their partner because of postpartum/menstruation (78.9%), tiredness/unwillingness (67.7%), partner's STI (64.1%), and his infidelity (62.7%). However, only 49.3% believed that they might refuse sex if the partner opposed condom use. Of the 171 sexually active participants, 78.4% had only one sexual partner. Condoms were the primary contraceptive used; however, 68.4% reported inconsistent condom use which was significantly associated with women's inability to buy condoms (aOR6.54, 95%CI:2.29-18.74), negotiate condom use (aOR6.11%CI:1.69-22.15), and being unmarried (aOR3.04, 95%CI:1.14-8.13). 33.3% self-reported a history/symptoms of STI which was significantly associated with new HIV-diagnosis (aOR=4.53, 95%CI=2.07-9.91), multiple sex-partners (aOR=4.25, 95%CI=1.73-10.43), lack of internet exposure (aOR=4.24, 95%CI=1.55-11.55), IPV (aOR=3.04, 95% CI=1.22-7.55), or unprotected sex (aOR=2.97, 95% CI=1.33-6.60). Conclusion The sexual health of WLHIV in Indonesia is affected by their relationship status, access to condoms, and ability to negotiate their use. Strategies focused on building a women's capability and support to defend their sexual rights are needed to improve the women's health, facilitate choice and reduce risk of onward HIV transmission. Disclosure No significant relationships.
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