Longitudinal IgA and IgG Response, and ACE2 Binding Blockade, to Full-Length SARS-CoV-2 Spike Protein Variants in a Population of Black PLWH Vaccinated with ChAdOx1 nCoV-19

Vaccines against SARS-CoV-2 have been pivotal in overcoming the COVID-19 pandemic yet understanding the subsequent outcomes and immunological effects remain crucial, especially for at-risk groups e.g., people living with human immunodeficiency virus (HIV) (PLWH). In this study we report the longitudinal IgA and IgG antibody titers, as well as antibody-mediated angiotensin converting enzyme 2 (ACE2) binding blockade, against the SARS-CoV-2 spike (S) proteins after 1 and 2 doses of the ChAdOx1 nCoV-19 vaccine in a population of Black PLWH. Here, we report that PLWH (N = 103) did not produce an anti-S IgA response after infection or vaccination, however, anti-S IgG was detected in response to vaccination and infection, with the highest level detected for infected vaccinated participants. The anti-IgG and ACE2 blockade assays revealed that both vaccination and infection resulted in IgG production, however, only vaccination resulted in a moderate increase in ACE2 binding blockade to the ancestral S protein. Vaccination with a previous infection results in the greatest anti-S IgG and ACE2 blockade for the ancestral S protein. In conclusion, PLWH produce an anti-S IgG response to the ChAdOx1 nCoV-19 vaccine and/or infection, and ChAdOx1 nCoV-19 vaccination with a previous infection produced more neutralizing antibodies than vaccination alone

Rubella seroprevalence in pregnant women living with and without HIV in Soweto, South Africa

OBJECTIVES: Rubella infection during pregnancy may cause foetal death or congenital rubella syndrome. In South Africa, the national public immunization programme does not include rubella vaccination. The aim of this study was to evaluate rubella sero-epidemiology in pregnant South African women living with and without HIV. METHODS: Serum samples obtained from women living with HIV (n=552) and without HIV (n=552) were tested for rubella immunoglobulin G antibodies using an ELISA. The proportions of women with seronegative titres (<8IU/ml) and seropositive titres (≥11IU/ml), and geometric mean titres (GMT) were compared by age group and HIV status. RESULTS: The overall proportion of rubella seropositivity was 97.8%. The proportion of seropositive women increased with age group (18-25 years: 97.0%; 26-32 years: 97.7%; 33-40 years: 99.3%; p=0.047 after adjusting for HIV status). Similar proportions of women living with and without HIV were seropositive. CONCLUSIONS: Rubella immunity was high among South African pregnant women living with and without HIV in the absence of rubella vaccination in the public immunization programme. However, a lower percentage of younger women had seropositive titres, indicating the need for routine rubella vaccination after an increase in vaccine coverage rates

T-cell responses induced by ChAdOx1 nCoV-19 (AZD1222) vaccine to wild-type severe acute respiratory syndrome coronavirus 2 among people with and without HIV in South Africa

Objective(s): This study aimed to investigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell responses 14 days after single-dose ChAdOx1 nCoV-19 (AZD1222) vaccination in black Africans with and without HIV in South Africa, as well as determine the effect of AZD1222 vaccination on cell-mediated immune responses in people with HIV (PWH) with prior SARS-CoV-2 infection. Methods: A total of 70 HIV-uninfected people and 104 PWH were prospectively enrolled in the multicentre, randomized, double-blinded, placebo-controlled, phase Ib/IIa trial (COV005). Peripheral blood mononuclear cells (PBMCs) were collected from trial participants 14 days after receipt of first dose of study treatment (placebo or AZD1222 vaccine). T-cell responses against the full-length spike (FLS) glycoprotein of wild-type SARS-CoV-2 and mutated S-protein regions found in the Alpha, Beta and Delta variants were assessed using an ex-vivo ELISpot assay. Results: Among AZD1222 recipients without preceding SARS-CoV-2 infection, T-cell responses to FLS of wild-type SARS-CoV-2 were similarly common in PWH and HIV-uninfected people (30/33, 90.9% vs. 16/21, 76.2%; P = 0.138); and magnitude of response was similar among responders (78 vs. 56 SFCs/106 PBMCs; P = 0.255). Among PWH, AZD1222 vaccinees with prior SARS-CoV-2 infection, displayed a heightened T-cell response magnitude compared with those without prior infection (186 vs. 78 SFCs/106 PBMCs; P = 0.001); and similar response rate (14/14, 100% vs. 30/33, 90.9%; P = 0.244). Conclusion: Our results indicate comparable T-cell responses following AZD1222 vaccination in HIV-uninfected people and PWH on stable antiretroviral therapy. Our results additionally show that hybrid immunity acquired through SARS-CoV-2 infection and AZD1222 vaccination, induce a heightened T-cell response

Estimated SARS-CoV-2 infection rate and fatality risk in Gauteng Province, South Africa : a population-based seroepidemiological survey

DATA AVAILABILITY : De-identified individual-level data and data sets generated during the current study are available for researchers who provide a methodologically sound proposal. If approved, the requestor must sign a data-use agreement. Additionally, the study protocol is available on request. All requests must be addressed to the corresponding author. Data will be available 3 months after publication of this manuscript.BACKGROUND : Limitations in laboratory testing capacity undermine the ability to quantify the overall burden of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. METHODS : We undertook a population-based serosurvey for SARS-CoV-2 infection in 26 subdistricts, Gauteng Province (population 15.9 million), South Africa, to estimate SARS-CoV-2 infection, infection fatality rate (IFR) triangulating seroprevalence, recorded COVID-19 deaths and excess-mortality data. We employed three-stage random household sampling with a selection probability proportional to the subdistrict size, stratifying the subdistrict census-sampling frame by housing type and then selecting households from selected clusters. The survey started on 4 November 2020, 8 weeks after the end of the first wave (SARS-CoV-2 nucleic acid amplification test positivity had declined to <10% for the first wave) and coincided with the peak of the second wave. The last sampling was performed on 22 January 2021, which was 9 weeks after the SARS-CoV-2 resurgence. Serum SARS-CoV-2 receptor-binding domain (RBD) immunoglobulin-G (IgG) was measured using a quantitative assay on the Luminex platform. RESULTS : From 6332 individuals in 3453 households, the overall RBD IgG seroprevalence was 19.1% [95% confidence interval (CI): 18.1–20.1%] and similar in children and adults. The seroprevalence varied from 5.5% to 43.2% across subdistricts. Conservatively, there were 2 897 120 (95% CI: 2 743 907–3 056 866) SARS-CoV-2 infections, yielding an infection rate of 19 090 per 100 000 until 9 January 2021, when 330 336 COVID-19 cases were recorded. The estimated IFR using recorded COVID-19 deaths (n = 8198) was 0.28% (95% CI: 0.27–0.30) and 0.67% (95% CI: 0.64–0.71) assuming 90% of modelled natural excess deaths were due to COVID-19 (n = 21 582). Notably, 53.8% (65/122) of individuals with previous self-reported confirmed SARS-CoV-2 infection were RBD IgG seronegative. CONCLUSIONS : The calculated number of SARS-CoV-2 infections was 7.8-fold greater than the recorded COVID-19 cases. The calculated SARS-CoV-2 IFR varied 2.39-fold when calculated using reported COVID-19 deaths (0.28%) compared with excess-mortality-derived COVID-19-attributable deaths (0.67%). Waning RBD IgG may have inadvertently underestimated the number of SARS-CoV-2 infections and conversely overestimated the mortality risk. Epidemic preparedness and response planning for future COVID-19 waves will need to consider the true magnitude of infections, paying close attention to excess-mortality trends rather than absolute reported COVID-19 deaths.The Bill and Melinda Gates Foundation.https://academic.oup.com/ijehj2023Family Medicin

ChAdOx1 nCoV-19 (AZD1222) vaccine-induced Fc receptor binding tracks with differential susceptibility to COVID-19

Despite the success of COVID-19 vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged that can cause breakthrough infections. Although protection against severe disease has been largely preserved, the immunological mediators of protection in humans remain undefined. We performed a substudy on the ChAdOx1 nCoV-19 (AZD1222) vaccinees enrolled in a South African clinical trial. At peak immunogenicity, before infection, no differences were observed in immunoglobulin (Ig)G1-binding antibody titers; however, the vaccine induced different Fc-receptor-binding antibodies across groups. Vaccinees who resisted COVID-19 exclusively mounted FcγR3B-binding antibodies. In contrast, enhanced IgA and IgG3, linked to enriched FcγR2B binding, was observed in individuals who experienced breakthrough. Antibodies unable to bind to FcγR3B led to immune complex clearance and resulted in inflammatory cascades. Differential antibody binding to FcγR3B was linked to Fc-glycosylation differences in SARS-CoV-2-specific antibodies. These data potentially point to specific FcγR3B-mediated antibody functional profiles as critical markers of immunity against COVID-19

Sero-epidemiology of measles Immunoglobulin G antibodies among newborn from South East Asia and sub-Saharan Africa: an observational, multicentre study.

ObjectivesTo investigate the transplacental acquisition of measles immunoglobulin (Ig)G in newborns at delivery in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa.MethodsArchived cord serum, from a multicenter study on Group B Streptococcus, were tested for measles IgG using a commercial enzyme link immunosorbent assay (ELISA). We tested 323 randomly selected samples from each of the sites. Models using various measles antibody decay rates in infancy were explored.ResultsOverall, 2,907 cord serum samples were analyzed. At birth, 49.9% of newborns were measles IgG seronegative. Measles seronegativity ranged from 21.7% in Nigeria to 73.4% in Bhutan. The adjusted odds of seronegativity in infants of mothers born after measles vaccination implementation was 1.78 times that for infants born to unvaccinated mothers (adjusted odds ratio 1.78; 95% confidence interval 1.43-2.21; P &lt;0.001). Modeling measles-IgG kinetics predicted that 70.8%, 88.3%, and 100% of infants would be seronegative by 2, 4, and 6 months, respectively, without further exposure.ConclusionsOur findings suggest low transplacental acquisition of measles IgG in newborns, which is likely to yield susceptibility to measles infection at a very young age. The currently recommended measles vaccine schedules in low- and middle-income countries (LMICs), with the first dose recommended from 9 months of age and onward, warrant reconsideration, including the need for earlier dosing schedules.</p

Prevalence of hepatitis B virus infection among pregnant women and cord blood hepatitis B surface antigen positive newborns in sub-Saharan Africa and South Asia

Background: Newborns infected with Hepatitis B Virus (HBV) are at risk of chronic liver disease and hepatocellular carcinoma. Objectives: This study investigated the prevalence of HBV infection among pregnant women and cord blood Hepatitis B surface antigen (HBsAg) positivity of their newborns in Bangladesh, Bhutan, India, Ethiopia, Mozambique, Kenya, Nigeria, Mali, and South Africa. Study design: Randomly selected paired maternal and cord blood samples (n = 101 each site) taken at delivery were tested for HBsAg and Hepatitis B extractable antigen (HBeAg) in the women using a chemiluminescent microparticle immunoassay. Similarly, cord blood sample of newborn was assessed for HBsAg reactivity. HBV DNA was quantified using the Xpert® HBV viral load assay, followed by genotyping. Results: The overall prevalence of maternal HBsAg positivity was 5.5 % (95 %CI: 0.4 %–7.1 %; n = 50/909). HBsAg positivity was higher in African countries (7.3 %; 95 %CI: 5.4 %–9.6 %; n = 44/606) compared to South Asian countries (2.0 %; 95 %CI: 0.8 %–4.3 %; n = 6/303; p = 0.002). Relative to South Africa, there were higher odds of HBsAg sero-positivity in women from Mozambique ((aOR): 7.7, 95 %CI: 1.6 %–37.8 %) and Mali (aOR: 5.7; 95 %CI: 1.1 %–29.7 %). The rate of HBsAg positivity in cord blood of babies born to HBsAg positive women was 28.0 % (95 %CI: 17.1 %–42.3 %; n = 14/50), including 31.8 % (95 %CI: 19.5–47.4 %; n = 14/44) in African countries. No cord blood HBsAg positivity was observed in South Asia. Genotypic analysis revealed HBV genotypes A (41.7 %) and E (58.3 %) were pre-dominant. Conclusion: The high rate of cord blood positivity (28.0 %) for HBsAg underscores the urgency of enhancing HBV prevention strategies to meet the World Health Organization's target of a 90 % reduction in new HBV infections by 2030.</p

Efficacy of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination against SARS-CoV-2 variants of concern: Final analysis of a randomized, placebo-controlled, phase 1b/2 study in South African adults (COV005)

COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18-65 years. South Africa's first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa's Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674

Combinatorial multimer staining and spectral flow cytometry facilitate quantification and characterization of polysaccharide-specific B cell immunity

Bacterial capsular polysaccharides are important vaccine immunogens. However, the study of polysaccharide-specific immune responses has been hindered by technical restrictions. Here, we developed and validated a high-throughput method to analyse antigen-specific B cells using combinatorial staining with fluorescently-labelled capsular polysaccharide multimers. Concurrent staining of 25 cellular markers further enables the in-depth characterization of polysaccharide-specific cells. We used this assay to simultaneously analyse 14 Streptococcus pneumoniae or 5 Streptococcus agalactiae serotype-specific B cell populations. The phenotype of polysaccharide-specific B cells was associated with serotype specificity, vaccination history and donor population. For example, we observed a link between non-class switched (IgM+) memory B cells and vaccine-inefficient S. pneumoniae serotypes 1 and 3. Moreover, B cells had increased activation in donors from South Africa, which has high-incidence of S. agalactiae invasive disease, compared to Dutch donors. This assay allows for the characterization of heterogeneity in B cell immunity that may underlie immunization efficacy