Waning antibody levels after COVID-19 vaccination with mRNA Comirnaty and inactivated CoronaVac vaccines in blood donors, Hong Kong, April 2020 to October 2021.

The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong's COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group's (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group's (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.

The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children.

Background: Children are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed. Methods: We tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS). Findings: Children have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

SARS-CoV-2 specific T cell responses are lower in children and increase with age and time after infection.

SARS-CoV-2 infection of children leads to a mild illness and the immunological differences with adults remains unclear. We quantified the SARS-CoV-2 specific T cell responses in adults and children (<13 years of age) with RT-PCR confirmed asymptomatic and symptomatic infection for long-term memory, phenotype and polyfunctional cytokines. Acute and memory CD4+ T cell responses to structural SARS-CoV-2 proteins significantly increased with age, whilst CD8+ T cell responses increased with time post infection. Infected children had significantly lower CD4+ and CD8+ T cell responses to SARS-CoV-2 structural and ORF1ab proteins compared to infected adults. SARS-CoV-2-specific CD8+ T cell responses were comparable in magnitude to uninfected negative adult controls. In infected adults CD4+ T cell specificity was skewed towards structural peptides, whilst children had increased contribution of ORF1ab responses. This may reflect differing T cell compartmentalisation for antigen processing during antigen exposure or lower recruitment of memory populations. T cell polyfunctional cytokine production was comparable between children and adults, but children had a lower proportion of SARS-CoV-2 CD4+ T cell effector memory. Compared to adults, children had significantly lower levels of antibodies to ß-coronaviruses, indicating differing baseline immunity. Total T follicular helper responses was increased in children during acute infection indicating rapid co-ordination of the T and B cell responses. However total monocyte responses were reduced in children which may be reflective of differing levels of inflammation between children and adults. Therefore, reduced prior ß-coronavirus immunity and reduced activation and recruitment of de novo responses in children may drive milder COVID-19 pathogenesis.

Cross-reactive antibody-dependent cellular cytotoxicity antibodies are increased by recent infection in a household study of influenza transmission.

OBJECTIVES: Influenza causes a spectrum of disease from asymptomatic infection to fatal outcome, and pre-existing immunity can alter susceptibility and disease severity. In a household transmission study, we recruited outpatients with confirmed influenza virus infection and prospectively identified secondary infections in their household contacts, therefore identifying infection cases with baseline samples for determining immune-mediated protection from influenza infection. METHODS: We examined baseline broadly reactive immune correlates of relevance to universal vaccine development, specifically antibody-dependent cytotoxic (ADCC) antibodies and T-cell responses in functional assays. Antibodies were assessed in a cell-based NK cell degranulation assay by flow cytometry, and T-cell responses were assessed by IFN-γ intracellular cytokine staining flow cytometry assay. RESULTS: The magnitude of antibody responses and ADCC function for multiple influenza-specific proteins was lower in participants who became infected, consolidating the role of pre-existing antibodies in protection from seasonal influenza virus infection. Among H1N1-infected contacts, we found that higher levels of pre-existing H1-haemagglutinin ADCC responses correlated with reduced symptom severity. Recent infection boosted the titre and magnitude of haemagglutinin-, neuraminidase- and nucleoprotein-specific ADCC antibodies. Limited T-cell samples precluded conclusions on the role of pre-existing T-cell responses. CONCLUSIONS: Overall, ADCC responses are a protective correlate against influenza virus infection that should be considered in future vaccine development and evaluation.Influenza-specific ADCC responses are elevated in uninfected subjects, associated with reduced symptoms and boosted by recent infection, whilst HA stem and NA IgG are also elevated in uninfected participants irrespective of ADCC function.

Early season estimate of influenza vaccination effectiveness against influenza hospitalisation in children, Hong Kong, winter influenza season 2018/19.

The winter 2018/19 influenza season in Hong Kong has been predominated by influenza A(H1N1)pdm09 as at January 2019. We enrolled 2,016 children in three public hospitals in Hong Kong between 2 September 2018 and 11 January 2019. Using the test-negative approach, we estimated high early season effectiveness of inactivated influenza vaccine against influenza A or B of 90% (95% confidence interval (CI): 80-95%) and 92% (95% CI: 82-96%) against influenza A(H1N1)pdm09.

Serum 25-Hydroxyvitamin D Was Not Associated with Influenza Virus Infection in Children and Adults in Hong Kong, 2009-2010.

BACKGROUND: Some studies have hypothesized that vitamin D may have a role to play in protection against influenza virus infections and illnesses, and that seasonal fluctuation in serum 25-hydroxyvitamin D [25(OH)D] may affect seasonal patterns of influenza virus infections. OBJECTIVE: We aimed to investigate whether serum 25(OH)D concentrations were associated with the incidence of influenza virus infections and illnesses in children and adults in Hong Kong. METHODS: In 2009-2010, 3030 children and adults of all ages from 796 households in Hong Kong were followed up to identify acute respiratory illnesses. Sera from 2694 participants were collected at baseline and after ∼1 mo, 6 mo, and 12 mo. Influenza virus infections were confirmed by reverse transcriptase-polymerase chain reaction performed on nasal and throat swab samples collected during illness episodes. Serologic evidence of influenza virus infection was measured by hemagglutination inhibition assays in unvaccinated participants. The serum 25(OH)D concentrations were measured after collection of all specimens. Each individual's baseline serum 25(OH)D concentration on 1 January 2010 was predicted by a random-effects linear regression model. RESULTS: We found that, in children and adults who had not received a seasonal influenza vaccine, baseline serum 25(OH)D concentrations (<50 nmol/L compared with ≥50 nmol/L) were not statistically significantly associated with serologic evidence of influenza A(H1N1)pdm09 (RR, 1.18; 95% CI: 0.85, 1.65) or seasonal influenza virus infections [including A(H3N2) and B virus] (RR, 1.13; 95% CI: 0.86, 1.49). In all participants, baseline serum 25(OH)D concentrations were not statistically significantly associated with polymerase chain reaction-confirmed influenza virus infection (RR, 1.15; 95% CI: 0.73, 1.83) and influenza-like illness (RR, 1.18; 95% CI: 0.98, 1.43). CONCLUSIONS: These findings indicate that lower serum vitamin D concentrations may not contribute to the seasonality of influenza and are not associated with an increased risk of influenza virus infections in persons of all ages in Hong Kong.

The global antigenic diversity of swine influenza A viruses.

Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans.

Hospitalization risk of the 2009 H1N1 pandemic cases in Hong Kong.

BACKGROUND: Reliable assessment for the severity of the 2009 H1N1 pandemic influenza is critical for evaluation of vaccination strategies for future pandemics. This study aims to estimate the age-specific hospitalization risks of the 2009 pandemic cases during the first wave in Hong Kong, by combining the findings from the serology and disease burden studies. METHODS: Excess hospitalization rates associated with the pandemic H1N1 were estimated from Poisson regression models fitted to weekly total numbers of non-accidental hospitalization from 2005 to 2010. Age-specific infection-hospitalization risks were calculated as excess hospitalization rates divided by the attack rates in the corresponding age group, which were estimated from serology studies previously conducted in Hong Kong. RESULTS: Excess hospitalization rate associated with pandemic H1N1 was highest in the 0-4 age group (881.3 per 100,000 population), followed by the 5-14, 60+, 15-29, 50-59, 30-39 and 40-49 age groups. The hospitalization risk of the infected cases (i.e. infection-hospitalization risk) was found highest in the 60+ age group and lowest in the 15-29 age group, with the estimates of 17.5% and 0.7%, respectively. CONCLUSIONS: People aged 60 or over had a relatively high infection-hospitalization risk during the first wave of the 2009 H1N1 pandemic, despite of a low attack rate in this age group. The findings support the policy of listing older people as the priority group for pandemic vaccination.