Older adults were disproportionately affected during the COVID-19 pandemic, and while many vaccine clinical trials included older adults, they failed to include those who were particularly old or frail. Immunosenescence, or the process of declining immune function with age, greatly affects susceptibility to infections. Evidence suggests that the effects of aging on the immune system differs between the sexes. Understanding immunosenescence is crucial for vaccine development and implementation in older populations to induce a robust immune response for protection against infectious disease. This study characterized the intersection of sex and aging on the antibody response to the Moderna and Pfizer COVID-19 vaccines.

To characterize the immune response in older adults, plasma samples were collected from vaccinees aged 75-98 years old before and after 3 doses and from younger adults aged 18-74 years old before and after 2 doses. Key antibody characteristics, such as antibody binding to antigens and virus neutralization, were measured against the vaccine virus and variants of concern (Alpha, Delta, and Omicron). Additionally, the established Fried frailty phenotype was used to assess participant’s frailty status.

Results of this research identified key differences in the immune response between females and males across the lifespan, as well as the impact of advanced age on vaccine-induced immunity. In both cohorts, vaccination induced a more robust antibody response in females compared to males. Furthermore, the younger cohort had higher measured antibody responses relative to the older cohort. Age and frailty were both associated with lower antibody response in males but interestingly, not in females. Older females also maintained higher antibody response to the variants of concern compared to older males. Antibody levels significantly declined in both older sexes 6 months post second dose but receiving a third dose replenished antibody response and eliminated sex, age, and frailty disparities. Taken together, these findings suggest that the third dose of mRNA vaccine is crucial to protect older adults from SARS-CoV-2 infection, particularly older frail males that may be more vulnerable.

Reference: Shapiro et al. Association of Frailty, Age, and Biological Sex with Severe Acute Respiratory Syndrome Coronavirus 2 messenger RNA Vaccine-Induced Immunity in Older Adults. Clin Infect Dis. 2022 Aug 15;75(Suppl 1):S61-S71.

This blog is cross-posted from HIV.gov. 

On Tuesday at the International AIDS Society’s 12th Conference on HIV Science (IAS 2023), HIV.gov continued our conversations about research highlights, including a focus on the latest about HIV vaccines. We also heard an update from the NIH Office of AIDS Research.

NIH’s Carl Dieffenbach, Ph.D., Director of the Division of AIDS at the National Institute of Allergy and Infectious Diseases (NIAID), spoke with Louis Shackelford, M.P.H., about HIV vaccine studies being discussed at IAS 2023 and potential roles for broadly neutralizing antibodies (or bNAbs). Louis is the Acting Director for External Relations at the NIH-supported HIV Vaccine Trials Network (HVTN) and COVID-19 Prevention Network. Noting it is an exciting time in HIV vaccine research, Carl explained that scientists are exploring how to take what we have learned about bNAbs, which prevented acquisition of some HIV strains, and turn that into an HIV vaccine. In addition, Carl and Louis discussed how bNAbs are being studied for use in HIV treatment and even, possibly, a cure. View their conversation below:

Bill Kapogiannis, M.D., Acting Director of NIH’s Office of AIDS Research (OAR), spoke with Catey Laube, Section Chief for HIV, STIs, Allergy, Immunology, and Transplantation in NIAID’s Office of Communications and Government Relations. OAR coordinates the scientific, budgetary, legislative, and policy components of HIV/AIDS research across NIH’s institutes and centers. Bill discussed the importance of the results from the NIH-supported REPRIEVE trial presented yesterday at the conference. The global study found that statins, a class of cholesterol-lowering medications, may offset the elevated risk of cardiovascular disease experienced by people with HIV by more than a third, potentially preventing one in five major cardiovascular events (e.g., heart attack or stroke) or premature deaths in this population. He noted that these important findings have implications for clinical guidelines for the care of people with HIV. Bill also observed that the findings are relevant to two of OAR’s signature programs: HIV and Aging, since the study population was people with HIV ages 40-75, and HIV and Women, since the results were equally applicable to women. View their conversation below:

IAS 2023, convening in Brisbane, Australia, features the latest advances in basic, clinical, and operational HIV research and seeks to move science into policy and practice. The conference features seven plenary sessions, more than 60 symposia and oral abstract sessions, hundreds of poster sessions, and many satellite sessions featuring highly diverse and cutting-edge research. Many of the studies that are being presented have been conducted by or funded by federal partners, including NIH, CDC, PEPFAR, DoD, and others.

As is the custom in Australia, HIV.gov acknowledges the Jagera and Turrbal people as the Traditional Custodians of Meanjin (Brisbane), the land on which IAS 2023 is taking place. We pay our respects to Jagera and Turrbal elders past, present, and emerging.

Follow all of our conversations from IAS 2023 this week here on the blog as well as on on HIV.gov’s Facebook, Instagram, and Twitter, and on the LinkedIn account of the HHS Office of Infectious Disease and HIV/AIDS Policy.

This blog is cross-posted from HIV.gov.

During the first full day of sessions at the International AIDS Society’s 12th Conference on HIV Science (IAS 2023), HIV.gov shared conversations on important study findings about reducing cardiovascular disease among people with HIV and the latest developments with long-acting prevention and treatment options that could one day become safe and effective alternatives to daily oral pills.

NIH’s Carl Dieffenbach discussed findings presented today about the NIH-supported Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) trial, a global study that demonstrated a daily statin medication reduces the increased risk of cardiovascular disease experienced by people living with HIV. (Learn more in this NIH news release published today.) Dr. Dieffenbach is the Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases (NIAID). He spoke today with Molly Moon, M.S.W., Deputy Director of the NIH-supported Office of HIV/AIDS Network Coordination. They also discussed progress reported at IAS 2023 from several studies investigating long-acting HIV prevention and treatment options, including some that were presented in a plenary session that Carl chaired today. Carl summarized that long-acting options are moving toward better drugs with lower doses and longer durations. View their conversation below:

To learn more about what the results of the REPRIEVE trial mean, Molly also spoke with Steven Grinspoon, M.D., professor of medicine at Harvard University and chief of the metabolism unit at Massachusetts General Hospital, who led the REPRIEVE study. Steven highlighted that this global trial, involving participants in 12 countries, found that the use of the statin pitavastatin calcium reduced the risk of major adverse cardiovascular events—including heart attack, stroke, and cardiovascular death—among people with HIV by 35%. He added that the study found that the intervention was equally efficacious among men and women. Simultaneous to their presentation at IAS 2023, the REPRIEVE study findings were published in the New England Journal of Medicine.

IAS 2023, convening in Brisbane, Australia, features the latest advances in basic, clinical, and operational HIV research and seeks to move science into policy and practice. The conference features seven plenary sessions, more than 60 symposia and oral abstract sessions, hundreds of poster sessions, and many satellite sessions featuring highly diverse and cutting-edge research. Many of the studies that will be presented have been conducted by or funded by federal partners, including NIH, CDC, PEPFAR, DoD, and others.

As is the custom in Australia, HIV.gov acknowledges the Jagera and the Turrbal people as the Traditional Custodians of Meanjin (Brisbane), the land on which IAS 2023 is taking place. We pay our respects to Jagera and Turrbal elders past, present, and emerging.

Follow all of our conversations from IAS 2023 this week on HIV.gov’s Facebook, Instagram, and Twitter, and on the LinkedIn account of the HHS Office of Infectious Disease and HIV/AIDS Policy.

Recurrent urinary tract infections (rUTI) affect people all around the world and contribute greatly to morbidity, especially for females. In the United States, over one million women seek medical care for rUTIs each year, which are most commonly caused by uropathogenic Escherichia coli (E. coli) and treated with antibiotics.  While history of a prior UTI is a significant risk factor, other drivers of rUTI remain unknown.  The impact of the microbiome on health and disease is being appreciated in other organ systems.  Therefore, this study explored the microbiome connection between the gut and the bladder, or the gut-bladder axis, by characterizing the direct and indirect influences of gut microbiota on the bladder, including the effects of antibiotics to the infection and microbiome.  

This longitudinal clinical study was conducted over the course of a year and enrolled women with a history of rUTI (3 or more UTIs in the past 12 months) and women with no history of UTIs for comparison. Blood, urine, and fecal samples were collected from all study participants for analysis. Fecal samples were taken monthly, and additional samples were collected during and post any UTI. Data collected were analyzed with multi-omics techniques to determine diversity of gut microbiota, biomarkers of immune states, and presence of E. coli strains. 

The results of the study showed noteworthy differences between women with rUTIs and their healthy counterparts that may inform future treatment options. Women with history of rUTI had less diversity in their gut microbiota and markers of low-level inflammation. Results also showed that women with history of rUTI have different immunological biomarkers compared to women in the healthy cohort, suggesting their immune systems could respond differently to treatment. The transmission of E.coli from gut to bladder was similar in both cohorts, but symptoms only occurred for the women with history of rUTI. However, it was found that the UTI-causing E.coli strains colonized the gut and remained even after antibiotic treatment, potentially explaining reoccurrence of UTIs only in some participants. Furthermore, repeated use of antibiotics may exacerbate gut-bladder imbalance.  

The currently used antibiotics and regimens used to treat UTIs and rUTIs may be propagating recurring infections. Antibiotic use reduced gut microbiome diversity and failed to permanently clear uropathogenic E.coli infection, potentially impacting gut-bladder health in women with rUTIs. More specific targeted use of antibiotics, like small molecule therapeutics, may help to improve infections while minimizing disruption to other gut microbiota. Further research is needed to better understand treatment options that also assist in restoring a healthy microbiome.  

Reference: Worby CJ, et al. Longitudinal multi-omics analyses link gut microbiome dysbiosis with recurrent urinary tract infections in women. Nat Microbiol. 2022 May;7(5):630-639. doi: 10.1038/s41564-022-01107-x. Epub 2022 May 2. PMID: 35505248 

Research by NIAID grantees strongly suggests that immune responses to a newly discovered species of gut bacteria may cause some cases of a common autoimmune disease called rheumatoid arthritis, or RA. The findings were recently published in Science Translational Medicine.

In people with RA, their own antibodies and T cells attack their joints, especially in the hands, wrists, and knees. This leads to inflammation, pain, and swelling in the joint lining. Over time, RA progresses to irreversible joint tissue damage, chronic pain, loss of function, and deformities. Scientists do not know what causes RA despite extensive efforts to understand the earliest stages of this disease.  

Some RA research has focused on understanding what triggers the development of the antibodies and T cells that attack the joints. Several studies have suggested that the production of joint-targeting antibodies starts at mucosal surfaces, such as the lining of the mouth, airways, and gut, more than a decade before symptoms arise and might be stimulated by bacteria at these sites. Until now, however, the bacterial culprit remained unknown.

In the new study, investigators isolated antibody-secreting cells called plasmablasts from the blood of people at risk for RA and found that the antibodies produced by these cells recognized certain bacteria in the gut microbiome of these individuals. The researchers identified a previously unknown bacterial species targeted by these antibodies, which they named Subdoligranulum didolesgii. This bacterium was present in the feces of four out of 24 people who were either at risk for or diagnosed with RA but absent from the feces of 12 healthy people.

The scientists hypothesized that a mucosal immune response to S. didolesgii in the gut might progress to a body-wide immune response. To test their hypothesis, the researchers gave mice an oral dose of the bacterium and monitored their immune and physical responses. The mice developed antibodies and T cells that attacked their joints and led to visible joint swelling. In addition, the immunologic changes that the scientists observed in the mice extended over time from the gut mucosa to sites throughout the body. 

Taken together, the findings suggest that in some people with RA, immune responses to S. didolesgii in the gut may trigger the production of antibodies and T cells that circulate throughout the body and attack the joints, leading to chronic inflammation. Thus, it appears that RA may develop because immune-system targets shared by S. didoglesgii and joint tissue have a similar structure or amino-acid sequence.

Didolesgi is the Cherokee word for arthritis or rheumatism and was proposed as the name for the newly discovered bacterium by the study’s first author, Meagan E. Chriswell, B.S., who is an enrolled member of the Cherokee Nation of Oklahoma. Ms. Chriswell, an M.D./Ph.D. candidate in immunology at the University of Colorado Anschutz Medical Campus in Aurora, and Kristine A. Kuhn, M.D., Ph.D., an associate professor of medicine at the university, led the research. 

The study was co-funded by NIAID and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, both part of the National Institutes of Health.

Reference: ME Chriswell, et al. Clonal IgA and IgG autoantibodies from individuals at risk for rheumatoid arthritis identify an arthritogenic strain of Subdoligranulum. Science Translational Medicine DOI: 10.1126/scitranslmed.abn5166 (2022).

To reduce the spread of HIV infection, the World Health Organization (WHO) recommends pre-exposure prophylaxis (PrEP) in populations with an annual HIV infection incidence greater than 3%. Given that the annual HIV incidence in Uganda is estimated at 0.40% (0.46% among females and 0.35% among males), there are people who may have a higher HIV risk and may benefit from PrEP but are not targeted for services. To further reduce the spread of HIV in Uganda, researchers used results from three survey rounds of HIV-negative participants within the Rakai Community Cohort Study (RCCS) to estimate the prevalence of high-risk individuals eligible for PrEP within the general population and the incidence of HIV infection associated with eligibility. 

In this study, a subset of questions from Uganda’s PrEP eligibility tool that are routinely asked within the RCCS surveys were used to determine PrEP eligibility. Eligibility was defined as reporting at least one of the following HIV risk behaviors in the past 12 months: sexual intercourse with more than one partner of unknown HIV status; nonmarital sex act without a condom; sex engagement in exchange for money, goods, or services; or experiencing genital ulcers. HIV incidence was estimated by analyzing seroconversion from HIV-negative to HIV-positive in participants who contributed to at least two of the survey rounds.

Overall, 29% of participants in the analysis met the eligibility criteria. Of these, 22% reported one HIV risk, 6% reported two HIV risks, and 1% reported three HIV risks. The results showed that PrEP eligible participants had twice the risk of acquiring HIV than their non-eligible counterparts. Furthermore, risk increased threefold in uncircumcised males but not circumcised males. Additionally, men who reported higher prevalence of risky behaviors had lower increase in HIV incidence compared to women, likely due to circumcision status and higher antiretroviral therapy coverage in HIV-infected females, leading to a decrease in transmission to men. The findings of this study support the use of PrEP eligibility screening in general populations with HIV incidence lower than 3% to reduce HIV acquisition even further in these populations.

Reference: Ssempijja et al. High Rates of Pre-exposure Prophylaxis Eligibility and Associated HIV Incidence in a Population With a Generalized HIV Epidemic in Rakai, Uganda, JAIDS Journal of Acquired Immune Deficiency Syndromes, July 1, 2022 - Volume 90 - Issue 3 - p 291-299.