Discrimination of primary and chronic cytomegalovirus infection based on humoral immune profiles in pregnancy.

BACKGROUND: Most humans have been infected by Cytomegalovirus (CMV) by the time they reach forty years of age. Whereas most of these CMV infections are well controlled by the immune system, congenital infection can lead to serious health effects and death for the fetus and neonate. Most humans have been infected bywith cytomegalovirus (CMV) by the time they reach mid-life without clinical signs of disease. However, in settings in which the immune system is undeveloped or compromised, the virus is not adequately controlled, and consequently presents a major infectious cause of both congenital disease during pregnancy as well as opportunistic infection in children and adults. With clear evidence that risk to the fetus is lower during chronic maternal infection, and varies in association with gestational age at the time of primary maternal infection, further research on humoral immune responses to primary CMV infection during pregnancy is needed. METHODS: Here, systems serology tools were applied to characterize antibody responses to CMV infection inamong pregnant and non-pregnant women experiencing either primary or chronic infection. RESULTS: Whereas strikingly different antibody profiles were observed depending on infection status, more limited differences were associated with pregnancy status. Beyond known differences in IgM responses that are used clinically for identification of primary infection, distinctions observed in IgA and FcγR- binding antibodiesy responses and among viral antigen specificities accurately predicted infection status in a cross-sectional cohort. Leveraging machine Machine learning, longitudinal samples were also was used to define an immunological clock of CMV infectionthe transition from primary to chronic states and predict time since primary infection with high accuracy. Humoral responses diverged over time in an antigen-specific manner, with IgG3 responses toward tegument decreasing over time as is typical of viral infections, while those directed to pentamer and glycoprotein B were lower during acute and greatest during chronic infection. CONCLUSION: In sum, this work provides new insights into the antibody response associated with CMV infection status in the context of pregnancy, revealing aspects of humoral immunity that have the potential to improve CMV diagnostics and to support clinical trials of interventions to reduce mother-to-fetus transmission of CMV. TRIAL REGISTRATION: Not applicable Funding. CYMAF consortium and National Institutes of Health.

Vaccine effectiveness against emerging COVID-19 variants using digital health data.

BACKGROUND: Participatory surveillance of self-reported symptoms and vaccination status can be used to supplement traditional public health surveillance and provide insights into vaccine effectiveness and changes in the symptoms produced by an infectious disease. The University of Maryland COVID Trends and Impact Survey provides an example of participatory surveillance that leveraged Facebook's active user base to provide self-reported symptom and vaccination data in near real-time. METHODS: Here, we develop a methodology for identifying changes in vaccine effectiveness and COVID-19 symptomatology using the University of Maryland COVID Trends and Impact Survey data from three middle-income countries (Guatemala, Mexico, and South Africa). We implement conditional logistic regression to develop estimates of vaccine effectiveness conditioned on the prevalence of various definitions of self-reported COVID-like illness in lieu of confirmed diagnostic test results. RESULTS: We highlight a reduction in vaccine effectiveness during Omicron-dominated waves of infections when compared to periods dominated by the Delta variant (median change across COVID-like illness definitions: -0.40, IQR[-0.45, -0.35]. Further, we identify a shift in COVID-19 symptomatology towards upper respiratory type symptoms (i.e., cough and sore throat) during Omicron periods of infections. Stratifying COVID-like illness by the National Institutes of Health's (NIH) description of mild and severe COVID-19 symptoms reveals a similar level of vaccine protection across different levels of COVID-19 severity during the Omicron period. CONCLUSIONS: Participatory surveillance data alongside methodologies described in this study are particularly useful for resource-constrained settings where diagnostic testing results may be delayed or limited.

Surveys that are sent out to users of social media can be used to supplement traditional methods to monitor the spread of infectious diseases. This has the potential to be particularly useful in areas where other data is unavailable, such as areas with less surveillance of infectious disease prevalence and access to infectious disease diagnostics. We used data from a survey available to users of the social media platform Facebook to collect information about any potential symptoms of COVID-19 infection and vaccines received during the COVID-19 pandemic. We found a potential reduction in vaccine effectiveness and change in symptoms when the Omicron variant was known to be circulating compared to the earlier Delta variant. This method could be adapted to monitor the spread of COVID-19 and other infectious diseases in the future, which might enable the impact of infectious diseases to be recognized more quickly.

COVID-19 Vaccine Acceptance and Uptake in Bangkok, Thailand: Cross-sectional Online Survey.

BACKGROUND: The third most severe COVID-19 wave in the middle of 2021 coincided with the dual challenges of limited vaccine supply and lagging acceptance in Bangkok, Thailand. Understanding of persistent vaccine hesitancy during the "608" campaign to vaccinate those aged over 60 years and 8 medical risk groups was needed. On-the-ground surveys place further demands on resources and are scale limited. We leveraged the University of Maryland COVID-19 Trends and Impact Survey (UMD-CTIS), a digital health survey conducted among daily Facebook user samples, to fill this need and inform regional vaccine rollout policy. OBJECTIVE: The aims of this study were to characterize COVID-19 vaccine hesitancy, frequent reasons for hesitancy, mitigating risk behaviors, and the most trusted sources of COVID-19 information through which to combat vaccine hesitancy in Bangkok, Thailand during the 608 vaccine campaign. METHODS: We analyzed 34,423 Bangkok UMD-CTIS responses between June and October 2021, coinciding with the third COVID-19 wave. Sampling consistency and representativeness of the UMD-CTIS respondents were evaluated by comparing distributions of demographics, 608 priority groups, and vaccine uptake over time with source population data. Estimates of vaccine hesitancy in Bangkok and 608 priority groups were tracked over time. Frequently cited hesitancy reasons and trusted information sources were identified according to the 608 group and degree of hesitancy. Kendall tau was used to test statistical associations between vaccine acceptance and vaccine hesitancy. RESULTS: The Bangkok UMD-CTIS respondents had similar demographics over weekly samples and compared to the Bangkok source population. Respondents self-reported fewer pre-existing health conditions compared to census data overall but had a similar prevalence of the important COVID-19 risk factor diabetes. UMD-CTIS vaccine uptake rose in parallel with national vaccination statistics, while vaccine hesitancy and degree of hesitancy declined (-7% hesitant per week). Concerns about vaccination side effects (2334/3883, 60.1%) and wanting to wait and see (2410/3883, 62.1%) were selected most frequently, while "not liking vaccines" (281/3883, 7.2%) and "religious objections" (52/3883, 1.3%) were selected least frequently. Greater vaccine acceptance was associated positively with wanting to "wait and see" and negatively with "don't believe I need (the vaccine)" (Kendall tau 0.21 and -0.22, respectively; adjusted P<.001). Scientists and health experts were most frequently cited as trusted COVID-19 information sources (13,600/14,033, 96.9%), even among vaccine hesitant respondents. CONCLUSIONS: Our findings provide policy and health experts with evidence that vaccine hesitancy was declining over the study timeframe. Hesitancy and trust analyses among the unvaccinated support Bangkok policy measures to address vaccine safety and efficacy concerns through health experts rather than government or religious officials. Large-scale surveys enabled by existing widespread digital networks offer an insightful minimal-infrastructure resource for informing region-specific health policy needs.

HIV-Associated Alterations of the Biophysical Features of Maternal Antibodies Correlate With Their Reduced Transfer Across the Placenta.

BACKGROUND: Human immunodeficiency virus (HIV) infection during pregnancy is associated with reduced transplacental transfer of maternal antibodies and increased risk of severe infections in children who are exposed and uninfected with HIV. The basis of this reduced transfer of maternal immunity has not yet been defined but could involve modifications in the biophysical features of antibodies. The objective of this study was to assess the impact of maternal HIV infection on the biophysical features of serum IgG and transplacental antibody transfer. METHODS: Maternal serum IgG subclass levels, Fc glycosylation, Fc receptor (FcR) binding, and transplacental transfer of pathogen-specific maternal IgG were measured in pregnant women with HIV (WWH) and pregnant women testing negative for HIV (WNH) in Cape Town, South Africa. RESULTS: Maternal antibody profiles were strikingly different between pregnant WWH and WNH. Antibody binding to FcγR2a and FcγR2b, IgG1 and IgG3 antibodies, and agalactosylated antibodies were all elevated in WWH, whereas digalactosylated and sialylated antibodies were reduced compared to pregnant WNH. Antibody features that were elevated in WWH were also correlated with reduced transplacental transfer of vaccine antigen-specific antibodies. CONCLUSIONS: HIV infection is associated with marked alterations of biophysical features of maternal IgG and reduced placental transfer, potentially impairing antimicrobial immunity.

Co-immunization of DNA and Protein in the Same Anatomical Sites Induces Superior Protective Immune Responses against SHIV Challenge.

We compare immunogenicity and protective efficacy of an HIV vaccine comprised of env and gag DNA and Env (Envelope) proteins by co-administration of the vaccine components in the same muscles or by separate administration of DNA + protein in contralateral sites in female rhesus macaques. The 6-valent vaccine includes gp145 Env DNAs, representing six sequentially isolated Envs from the HIV-infected individual CH505, and matching GLA-SE-adjuvanted gp120 Env proteins. Interestingly, only macaques in the co-administration vaccine group are protected against SHIV CH505 acquisition after repeated low-dose intravaginal challenge and show 67% risk reduction per exposure. Macaques in the co-administration group develop higher Env-specific humoral and cellular immune responses. Non-neutralizing Env antibodies, ADCC, and antibodies binding to FcγRIIIa are associated with decreased transmission risk. These data suggest that simultaneous recognition, processing, and presentation of DNA + Env protein in the same draining lymph nodes play a critical role in the development of protective immunity.