Dobano, C. | Search bioRxiv

bioRxiv2020

Reduced placental transfer of antibodies against microbial and vaccine antigens in HIV-infected women in Mozambique

Antibody transplacental transfer is essential for conferring protection in newborns against infectious diseases. This transfer may be affected by gestational age and maternal infections, although the effects are not consistent across studies. We measured total IgG and IgG subclasses by quantitative suspension array technology against fourteen pathogens and vaccine antigens, including target of maternal immunization, in 341 delivering HIV- and HIV+ mother-infant pairs from southern Mozambique. Maternal antibody levels were the main determinant of cord antibody levels. HIV broadly reduced the placental transfer and cord levels of IgG and IgG1, but also IgG2 to half of the antigens. Plasmodium falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer but this was antigen-subclass dependent. These findings suggest maternal infections may impact the efficacy of maternal immunization and confirm the lower transfer of antibodies as one of the causes underlying increased susceptibility to infections in HIV-exposed infants.

immunology↗

bioRxiv2020

Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens

Reliable serological tests are required to determine the prevalence of antibodies against SARS-CoV-2 antigens and to characterise immunity to the disease in order to address key knowledge gaps in the context of the COVID-19 pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and ELISA with their higher precision, dynamic range, throughput, miniaturization, cost-efficacy and multiplexing capacity. We developed three qSAT assays to detect IgM, IgA and IgG to a panel of eight SARS-CoV-2 antigens including spike (S), nucleoprotein (N) and membrane (M) protein constructs. The assays were optimized to minimize processing time and maximize signal to noise ratio. We evaluated the performance of the assays using 128 plasmas obtained before the COVID-19 pandemic (negative controls) and 115 plasmas from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 8 were asymptomatic, 58 had mild symptoms and 49 were hospitalized. Pre-existing IgG antibodies recognizing N, M and S2 proteins were detected in negative controls suggestive of cross-reactive to common cold coronaviruses. The best performing antibody isotype/antigen signatures had specificities of 100% and sensitivities of 94.94% at [≥]14 days since the onset of symptoms and 96.08% at [≥]21 days since the onset of symptoms, with AUC of 0.992 and 0.999, respectively. Combining multiple antibody markers as assessed by qSAT assays has the highest efficiency, breadth and versatility to accurately detect low-level antibody responses for obtaining reliable data on prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity required for vaccine development to combat pandemics like the COVID-19.

immunology↗