Effectiveness of a monovalent human rotavirus vaccine among children of 5 years and under in KwaZulu-Natal.

Doctor of Philosophy in Medical Microbiology. University of KwaZulu-Natal, Medical School 2016.Human rotavirus infection is the leading cause of gastroenteritis in infants and young children worldwide. In South Africa, gastroenteritis is a major cause of childhood morbidity and mortality in children less than 5 years, and rotavirus infection has been documented as causing one-third of all gastroenteritis related hospital admissions. Vaccination is the major public health intervention to control rotavirus disease. The Rotarix® is the only rotavirus vaccine included in the national immunization program of South Africa. The effectiveness of this vaccine is questionable due to the continual outbreaks of rotavirus infection in South Africa, including KwaZulu-Natal, regardless of the high vaccination coverage. This study focused on evaluating the factors influencing the effectiveness of the Rotarix® vaccine in children 5 years and under in KwaZulu-Natal, South Africa. After obtaining written informed consent from parents or guardians, stool and blood specimens where collected from children 5 years and under presenting to King Edward VIII hospital (KEH VIII) in Durban, South Africa. The study was conducted between June 2014 and June 2015. Demographic and clinical information was collected using a well-structured questionnaire. Enzyme immunoassay (EIA) was performed to detect rotavirus antigen in the stool and rotavirus immunoglobulin G (IgG) in the serum. Selected EIA positive and negative samples were confirmed using G-types and P-types consensus primers in a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The RT-PCR positives were genotyped using genotypes specific primers. The avidity of the rotavirus specific IgG was determined using the urea elution technique. Rotarix® vaccines stored at optimum temperatures were collected from the provincial pharmaceutical store. The effect of sub-optimal temperatures on the potency of the Rotarix® vaccine were determined using the plaque assay. Three hundred and sixty-five (365) stool specimens were collected. Rotavirus antigen was detected in 83 (22.7%) patients from stool specimens. The stratification of rotavirus cases by vaccination status was not significant (p=0.4). The distribution of rotavirus was not significantly associated with HIV status of the children (p=0.7). We observed that seasonality was a significant driving force influencing the prevalence of rotavirus infection in our setting (p<0.001). We recorded the highest rotavirus prevalence in the winter months of the year with 79 (45.9%) positive cases of rotavirus associated diarrhoea. Blood specimens were only collected in 35 patients. From the corresponding stool specimens [21 (60%) EIA positives and 14 (40%) EIA negatives)], 29 (82.9%) were positive for rotavirus using conventional RT-PCR. Genotyping revealed G9P[8] (20.7%) to be the most prevalent genotype followed by G9P[4] (13.8%), G12P[4] (10.3%), G9P[6] (6.9%) and a 3.4% prevalence was recorded for each of G4/G8P[6], G4P[6], G12P[6], G8P[10] and G9P[10]. We were unable to fully genotype some of the rotavirus strains (non-typeable) by the available primers. 2 (6.9%) and 4 (13.8%) were non-typeable for the G and P types respectively. However, all 35 serum samples were positive for rotavirus IgG. We observed that the rotavirus specific IgG had no significant effect on the prevalence of rotavirus detection in stool (p=0.8). There was no significant difference in the mean avidity of IgG in the 3 vaccination strata (p=0.3). Exposure of the Rotarix® vaccine to the seasonal temperatures and to extreme temperatures of 40oC for 3 to 72 hours as well as -20oC and -80oC for 12 hours did not affect the potency of the vaccine beyond its expected standard. Our study highlighted the genetic diversity of rotaviruses and poor immunogenicity of the vaccine as key factors affecting the effectiveness of the rotavirus vaccine. Whether the vaccine is able to induce homotypic and heterotypic protection in immunized children is critical in predicting the long range effectiveness of this vaccine against uncommon regional rotavirus strains. Interventions targeted at improving socio-economic conditions in low income countries might be a starting point towards the control and prevention of rotavirus infection in these settings

Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa

Background: Rotavirus infection and its associated hospitalization of children less than 5 years old in middle- and low-income countries remains a public health challenge. We hypothesized that the Rotarix®potency is affected by non-optimal temperatures which translates into reduced vaccine effectiveness in these settings.Objective: To assess the effect of non-optimal temperatures on the potency of the Rotarix® vaccine in South Africa.Methods: Rotarix® vaccine was exposed to temperatures reflecting breaches in the cold chain. Vero cells (ATCC CCL-81) grown in a 24-well tissue culture plates were infected with Rotarix® vaccine viruses after exposure to non-optimal temperatures and the potency of the vaccine was determined using the plaque assay. Results: Exposure of the Rotarix® vaccine to seasonal temperatures in KwaZulu-Natal for 6 hours and to extreme temperatures of 40oC for 72 hours as well as to -20oC and -80oC for 12 hours did not affect the potency of the vaccine beyond its expected standard of &gt;7 x 105 PFU/ml.Conclusion: This study revealed that the Rotarix® vaccine remains potent even after exposure to non-optimal temperatures. However, this study only explored the effect of a constant ‘adverse’ temperature on vaccine potency and not the effect of temperature fluctuations.Keywords: Monovalent rotavirus vaccine, KwaZulu-Natal, South Africa

Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa

Background: Rotavirus infection and its associated hospitalization of children less than 5 years old in middle- and low-income countries remains a public health challenge. We hypothesized that the Rotarix\uaepotency is affected by non-optimal temperatures which translates into reduced vaccine effectiveness in these settings. Objective: To assess the effect of non-optimal temperatures on the potency of the Rotarix\uae vaccine in South Africa. Methods: Rotarix\uae vaccine was exposed to temperatures reflecting breaches in the cold chain. Vero cells (ATCC CCL-81) grown in a 24-well tissue culture plates were infected with Rotarix\uae vaccine viruses after exposure to non-optimal temperatures and the potency of the vaccine was determined using the plaque assay. Results: Exposure of the Rotarix\uae vaccine to seasonal temperatures in KwaZulu-Natal for 6 hours and to extreme temperatures of 40oC for 72 hours as well as to -20oC and -80oC for 12 hours did not affect the potency of the vaccine beyond its expected standard of &gt;7 x 105 PFU/ml. Conclusion: This study revealed that the Rotarix\uae vaccine remains potent even after exposure to non-optimal temperatures. However, this study only explored the effect of a constant \u2018adverse\u2019 temperature on vaccine potency and not the effect of temperature fluctuations. DOI: https://dx.doi.org/10.4314/ahs.v19i2.22 Cite as: Asowata OE, Ashiru OT, Sturm AW, Moodley P. Stability of a monovalent rotavirus vaccine after exposure to different temperatures observed in KwaZulu-Natal, South Africa. Afri Health Sci.2019;19(2): 1993-1999. https://dx.doi.org/10.4314/ahs.v19i2.2

Innate Lymphoid Cell Activation and Sustained Depletion in Blood and Tissue of Children Infected with HIV from Birth Despite Antiretroviral Therapy

Innate lymphoid cells (ILCs) are important for response to infection and for immune development in early life. HIV infection in adults depletes circulating ILCs, but the impact on children infected from birth remains unknown. We study vertically HIV-infected children from birth to adulthood and find severe and persistent depletion of all circulating ILCs that, unlike CD4+ T cells, are not restored by long-term antiretroviral therapy unless initiated at birth. Remaining ILCs upregulate genes associated with cellular activation and metabolic perturbation. Unlike HIV-infected adults, ILCs are also profoundly depleted in tonsils of vertically infected children. Transcriptional profiling of remaining ILCs reveals ongoing cell-type-specific activity despite antiretroviral therapy. Collectively, these data suggest an important and ongoing role for ILCs in lymphoid tissue of HIV-infected children from birth, where persistent depletion and sustained transcriptional activity are likely to have long-term immune consequences that merit further investigation

HIV specific CD8+ TRM-like cells in tonsils express exhaustive signatures in the absence of natural HIV control

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue-resident memory (TRM) CD8+ T-cells is of great interest, but limited data exist on TRM-like cells within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and a transcriptionally TRM-like profile distinct from blood CD8+ T-cells. In PLWH, CD8+ TRM-like cells are expanded and adopt a more cytolytic, activated, and exhausted phenotype not reversed by antiretroviral therapy (ART). This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood suggesting a higher antigen burden in tonsils. Single-cell transcriptional and clonotype resolution showed that these HIV-specific CD8+ T-cells in the tonsils express heterogeneous signatures of T-cell activation, clonal expansion, and exhaustion ex-vivo. Interestingly, this signature was absent in a natural HIV controller, who expressed lower PD-1 and CXCR5 levels and reduced transcriptional evidence of T-cell activation, exhaustion, and cytolytic activity. These data provide important insights into lymphoid tissue-derived HIV-specific CD8+ TRM-like phenotypes in settings of HIV remission and highlight their potential for immunotherapy and targeting of the HIV reservoirs

HIV Prevention in a Time of COVID-19: A Report from the HIVR4P // Virtual Conference 2021.

The HIV Research for Prevention (HIVR4P) conference catalyzes knowledge sharing on biomedical HIV prevention interventions such as HIV vaccines, antibody infusions, pre-exposure prophylaxis, and microbicides in totality-from the molecular details and delivery formulations to the behavioral, social, and structural underpinnings. HIVR4P // Virtual was held over the course of 2 weeks on January 27-28 and February 3-4, 2021 as the coronavirus disease 2019 (COVID-19) pandemic continued to inflict unprecedented harm globally. The HIVR4P community came together with 1,802 researchers, care providers, policymakers, implementers, and advocates from 92 countries whose expertise spanned the breadth of the HIV prevention pipeline from preclinical to implementation. The program included 113 oral and 266 poster presentations. This article presents a brief summary of the conference highlights. Complete abstracts, webcasts, and daily rapporteur summaries may be found on the conference website (https://www.hivr4p.org/)

Will Africans take COVID-19 vaccination?

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online crosssectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences.http://www.plosone.orgam2022Veterinary Tropical Disease

Will Africans take COVID-19 vaccination?

The economic and humanistic impact of COVID-19 pandemic is enormous globally. No definitive treatment exists, hence accelerated development and approval of COVID-19 vaccines, offers a unique opportunity for COVID-19 prevention and control. Vaccine hesitancy may limit the success of vaccine distribution in Africa, therefore we assessed the potentials for coronavirus vaccine hesitancy and its determinants among Africans. An online cross-sectional African-wide survey was administered in Arabic, English, and French languages. Questions on demographics, self-reported health status, vaccine literacy, knowledge and perception on vaccines, past experience, behavior, infection risk, willingness to receive and affordability of the SARS-COV-2 vaccine were asked. Data were subjected to descriptive and inferential statistics. A total of 5,416 individuals completed the survey. Approximately, 94% were residents of 34 African countries while the other Africans live in the Diaspora. Only 63% of all participants surveyed were willing to receive the COVID-19 vaccination as soon as possible and 79% were worried about its side effects. Thirty-nine percent expressed concerns of vaccine-associated infection. The odds of vaccine hesitancy was 0.28 (95% CI: 0.22, 0.30) among those who believed their risk of infection was very high, compared to those who believed otherwise. The odds of vaccine hesitancy was one-fifth (OR = 0.21, 95% CI: 0.16, 0.28) among those who believed their risk of falling sick was very high, compared to those who believed their risk of falling very sick was very low. The OR of vaccine hesitancy was 2.72 (95% CI: 2.24, 3.31) among those who have previously refused a vaccine for themselves or their child compared to counterparts with no self-reported history of vaccine hesitancy. Participants want the vaccines to be mandatory (40%), provided free of charge (78%) and distributed in homes and offices (44%). COVID-19 vaccine hesitancy is substantial among Africans based on perceived risk of coronavirus infection and past experiences

Unbiased Profiling Reveals Compartmentalization of Unconventional T-Cells Within the Intestinal Mucosa Irrespective of HIV Infection

The intestinal mucosa is enriched for unconventional T-cells, including mucosal associated invariant T-cells (MAIT), invariant natural killer T-cells (iNKT) and gamma delta T-cells. These cells are activated by bacterial metabolites, lipid antigens and cytokines, and are important for intestinal barrier integrity. The loss of gut homeostasis observed in HIV infection is central to disease pathogenesis, and studies have highlighted impairment of particular unconventional T-cell subsets within a specific gut compartment. However, although the small and large intestine are distinct niches, the overall impact of HIV on unconventional T-cells across the gut mucosal has not been well-studied. We hypothesized that compartment specific differences in the unconventional T-cell repertoire would exist between the small and large intestine, due to increasing bacterial loads and microbial diversity;and that the impact of HIV infection might differ depending on the compartment examined. We used mass cytometry, flow cytometry and unbiased T-cell receptor profiling to quantify unconventional T-cells in blood and tissue from the small (duodenum) and large (colon) intestine in HIV infected and uninfected participants undergoing examination for a range of intestinal conditions. Overall, we find distinct compartmentalisation of T-cells between blood, duodenum and colon, with iNKT cells significantly enriched in the duodenum and delta-1 expressing gamma delta T-cells in the colon. In addition, we observe greater clonal expansion of conventional TCRs in the duodenum, suggestive of stronger adaptive immunity in this compartment. Conversely, we find evidence of an expanded unconventional TCR repertoire in the colon, which contained far more overlapping "donor unrestricted" sequences than the duodenum. Twelve of these TCRs were highly "MAIT-like" and 3 were unique to the colon, suggesting an enrichment of donor unrestricted T-cells (DURTs) in this compartment. Unexpectedly, however, no significant impact of HIV infection on any of the unconventional T-cell subsets measured was observed in either mucosal site in terms of frequency or TCR repertoire. Further studies are required to investigate the importance of these unconventional T-cell subsets to intestinal homeostasis within the different gut compartments and determine if they are functionally impaired during HIV infection