ABSTRACT
BackgroundThere is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease. MethodsThis prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for M[a]ori, Pacific peoples, older adults [≥] 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.1 strains using a surrogate viral neutralisation assay. Results285 adults with median age of 52 years were included. 55% were female, 30% were M[a]ori, 28% were Pacific peoples, and 26% were [≥]65 years of age. Obesity, cardiac and pulmonary disease and diabetes were more common than in the general population. All participants received 2 doses of BNT162b2 vaccine. At 28 days after second vaccination, 99.6% seroconverted to the vaccine, and anti-S IgG and neutralising antibody levels were high across gender and ethnic groups. IgG and neutralising responses declined with age. Lower responses were associated with age [≥]75 and diabetes, but not BMI. The ability to neutralise the Omicron BA.1 variant in vitro was severely diminished but maintained against other variants of concern. ConclusionsVaccine antibody responses to BNT162b2 were generally robust and consistent with international data in this COVID-19 naive cohort with representation of key populations at risk for COVID-19 morbidity. Subsequent data on response to boosters, durability of responses and cellular immune responses should be assessed with attention to elderly adults and diabetics.
ABSTRACT
During the first wave of SARS-CoV-2 infection in New Zealand a cohort of 78 PCR-confirmed COVID-19 cases was recruited in the Southern District Health Board region. Here we report on this unique cohort nearly 1-year after infection. There was no known community transmission in the region over the study period due to New Zealands elimination status at the time, nor had any participants received a COVID-19 vaccine. In the absence of re-exposure, antibody reactivity to the viral spike protein, as well as neutralising antibodies to both the ancestral strain and the delta variant remained relatively stable between 8 and 11 months post-infection. This suggests long-lived antibody responses can be generated from a single natural infection event. However, given the risks of serious disease associated with SARS-CoV-2 infection, vaccination is still strongly recommended.
ABSTRACT
Estimating the longevity of an individual's immune response to the Sars-Cov-2 virus is vital for future planning, particularly of vaccine requirements. Neutralising antibodies (Nabs) are increasingly being recognised as a correlate of protection and whilst there are many studies which follow the response of a cohort of people, each study alone is not enough to predict the long term response. Studies use different assays to measure Nabs making them hard to combine. We present a modelling method which can combine multiple datasets and can be updated as more detailed data becomes available. Combining data from six published datasets we predict that after a short period of rapid decay the half-life of the NAb response is approximately one year giving optimism that the response will be long-lived.
ABSTRACT
A large-scale SARS-CoV-2 serosurvey of New Zealand blood donors (n=9806) was conducted at the end of 2020. Seroprevalence, after adjusting for test sensitivity and specificity, was very low (0.1%). This finding is consistent with limited community transmission and provides robust evidence to support New Zealand s successful elimination strategy for COVID-19.
ABSTRACT
ObjectivesCirculating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealands successful elimination strategy. MethodsA triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3, IgG4) responses against Nucleocapsid (N) protein, Receptor Binding Domain (RBD) and Spike (S) protein of SARS-CoV-2 was developed. After establishing baseline levels with pre-pandemic control sera (n=113), samples from PCR-confirmed COVID-19 patients with mild-moderate disease (n=189) collected up to eight months post-infection were examined. The relationship between antigen-specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE-2 interaction. ResultsWhile most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4-8 months post-infection. Anti-RBD antibodies were strongly correlated with NAbs at all time points (Pearsons r [≥] 0.87) and feasibility of using finger prick sampling to accurately measure anti-RBD IgG was demonstrated. ConclusionAntibodies to SARS-CoV-2 persist for up to eight months following mild to moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.
ABSTRACT
BackgroundDuring New Zealands first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. PCR testing was initially limited by a narrow case definition and limited laboratory capacity, so cases may have been missed. ObjectivesTo evaluate the Abbott(R) SARS-CoV-2 IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies among PCR-confirmed and probable cases, contacts, and higher risk individuals in the Southern Region of NZ. Study designPre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity. For prevalence analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR-confirmed cases (n=78), probable cases (n=9), and higher risk individuals with grey-zone (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays. ResultsThe median time from infection onset to serum collection for PCR-confirmed cases was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI, 98.2%-99.99%) and a sensitivity of 76.9% (95% CI, 66.0%-85.7%). Spike-based assays demonstrated superior sensitivity ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors. ConclusionsSpike-based assays demonstrated higher sensitivity than the Abbott IgG assay, likely due to temporal differences in antibody persistence. No unexpected SARS-CoV-2 infections were found in the Southern region of NZ, supporting the elimination status of the country at the time this study was conducted.
ABSTRACT
Pro-inflammatory immune responses are necessary for effective pathogen clearance, but cause severe tissue damage if not shut down in a timely manner1,2. Excessive complement and IFN-{gamma}-associated responses are known drivers of immunopathogenesis3 and are among the most highly induced immune programs in hyper-inflammatory SARS-CoV2 lung infection4. The molecular mechanisms that govern orderly shutdown and retraction of these responses remain poorly understood. Here, we show that complement triggers contraction of IFN-{gamma} producing CD4+ T helper (Th) 1 cell responses by inducing expression of the vitamin D (VitD) receptor (VDR) and CYP27B1, the enzyme that activates VitD, permitting T cells to both activate and respond to VitD. VitD then initiates the transition from pro-inflammatory IFN-{gamma}+ Th1 cells to suppressive IL-10+ Th1 cells. This process is primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating superenhancers and recruiting c-JUN and BACH2, a key immunoregulatory transcription factor5-7. Accordingly, cells in psoriatic skin treated with VitD increased BACH2 expression, and BACH2 haplo-insufficient CD4+ T cells were defective in IL-10 production. As proof-of-concept, we show that CD4+ T cells in the bronchoalveolar lavage fluid (BALF) of patients with COVID-19 are Th1-skewed and that VDR is among the top regulators of genes induced by SARS-CoV2. Importantly, genes normally down-regulated by VitD were de-repressed in CD4+ BALF T cells of COVID-19, indicating that the VitD-driven shutdown program is impaired in this setting. The active metabolite of VitD, alfacalcidol, and cortico-steroids were among the top predicted pharmaceuticals that could normalize SARS-CoV2 induced genes. These data indicate that adjunct therapy with VitD in the context of other immunomodulatory drugs may be a beneficial strategy to dampen hyperinflammation in severe COVID-19.
