Hepatitis B virus (HBV): serological markers of infection and immunity in a cohort of South African children

Children age 6-60 months were recruited as part of the Co-infection in South-African Children (COSAC) study, in Kimberley, South Africa. HIV-negative participants (n=174) were recruited through the Kimberley Respiratory Cohort (KReC). These children were admitted to hospital with a clinical diagnosis of respiratory tract infection between July 2014 and August 2016. HIV-positive children (n=136) were recruited primarily from HIV outpatient clinics, (recruited between September 2009 and July 2016). Children had research blood samples taken at the same time as routine clinical blood tests. We tested all samples for markers of hepatitis B virus (HBV) infection and immunity. HBsAg testing was carried out in Kimberley Hospital, South Africa using the Magnetic parcel chemiluminometric immunoassay (MPCI; Advia Centaur platform). Confirmatory HBsAg testing, together with anti-HBs and anti-HBc testing, was carried out by the microbiology department at Oxford University Hospitals (OUH) NHS Foundation Trust, Oxford, UK (Architect i2000). Ethics approval for this study was obtained from the Ethics Committee of the Faculty of Health Science, University of the Free State, Bloemfontein, South Africa (HIV Study Ref: ETOVS Nr 08/09 and COSAC Study Ref: ECUFS NR 80/2014). Written consent for enrollment into the study was obtained from the child’s parent or guardian

Linear correlation between (A) NucliSens v2.0 versus CAP/CTM v2.0 (B) NucliSens v2.0 versus Amplicor v1.5 (C) CAP/CTM v2.0 versus Amplicor v1.5.

<p>Solid lines represent the fitted linear regression curve, dashed lines show the equality line and dotted lines represent lower limits of detection of the respective assay.</p

Bland-Altman model showing the agreement between (A) NucliSens v2.0 and CAP/CTM v2.0 (B) NucliSens v2.0 and Amplicor v1.5 (C) CAP/CTM v2.0 and Amplicor v1.5.

<p>Dashed horizontal lines show the mean difference and the dotted lines indicate the 95% limits of agreement.</p

Data summary for viral load results as determined by the Amplicor v1.5, NucliSens v2.0 and CAP/CTM v2.0 assay.

<p>Data summary for viral load results as determined by the Amplicor v1.5, NucliSens v2.0 and CAP/CTM v2.0 assay.</p

Table_1_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.xlsx

IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p

Cohort characteristics.

<p>Cohort characteristics.</p

Image_2_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.jpeg

IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p

Image_4_Age- and sex-specific differences in immune responses to BNT162b2 COVID-19 and live-attenuated influenza vaccines in UK adolescents.jpeg

IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12–16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS–CoV–2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS–CoV–2-specific IgG and neutralising antibodies and cellular immunity specific for SARS–CoV–2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS–CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32–52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV–2 previously infected, 743,691 vs. 269,985; p DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.</p

HLA associations with the remaining 15-mer OLP’s in CMV pp65, IE-1 and IE-2 that were targeted by ≥4% of the study cohort.

<p>HLA associations with the remaining 15-mer OLP’s in CMV pp65, IE-1 and IE-2 that were targeted by ≥4% of the study cohort.</p

Immunodominant CMV-specific CD8+ T-cell responses within pp65, IE-1 and IE-2 measured by IFN-g ELISpot assay for CMV+ subjects.

<p>(A) Percentage responders to each protein-covering peptide pool. (B) Percentage responders among 152 CMV+ individuals to pp65 15mer overlapping peptides that were targeted by >4% of the study population. (C) Percentage responders among 95 CMV+ individuals to IE-1 15mer overlapping peptides that were targeted by >3% of the study population. (D) Percentage responders among 92 CMV+ individuals to IE-2 15mer overlapping peptides that were targeted by >3% of the study population.</p