Lipid nanoparticle mRNA vaccines are an exciting but emerging technology used in humans. There is limited understanding of the factors that influence their biodistribution and immunogenicity. Antibodies to poly(ethylene glycol) (PEG), which is on the surface of the lipid nanoparticle, are detectable in humans and boosted by human mRNA vaccination.
View Article and Find Full Text PDFMucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs).
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection of vaccinated individuals is increasingly common with the circulation of highly immune evasive and transmissible Omicron variants. Here, we report the dynamics and durability of recalled spike-specific humoral immunity following Omicron BA.1 or BA.
View Article and Find Full Text PDFAlthough the protective role of neutralizing antibodies against COVID-19 is well established, questions remain about the relative importance of cellular immunity. Using 6 pMHC multimers in a cohort with early and frequent sampling, we define the phenotype and kinetics of recalled and primary T cell responses following Delta or Omicron breakthrough infection in previously vaccinated individuals. Recall of spike-specific CD4 T cells was rapid, with cellular proliferation and extensive activation evident as early as 1 day post symptom onset.
View Article and Find Full Text PDFVaccination against SARS-CoV-2 protects from infection and improves clinical outcomes in breakthrough infections, likely reflecting residual vaccine-elicited immunity and recall of immunological memory. Here, we define the early kinetics of spike-specific humoral and cellular immunity after vaccination of seropositive individuals and after Delta or Omicron breakthrough infection in vaccinated individuals. Early longitudinal sampling revealed the timing and magnitude of recall, with the phenotypic activation of B cells preceding an increase in neutralizing antibody titers.
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit CD4 T cell responses to the spike protein, including circulating follicular helper T (cT) cells that correlate with neutralizing antibodies. Using a novel HLA-DRB1*15:01/S tetramer to track spike-specific CD4 T cells, we show that primary infection or vaccination induces robust S-specific CXCR5 and cT cell memory responses. Secondary exposure induced recall of CD4 T cells with a transitory CXCR3 phenotype, and drove expansion of cT cells transiently expressing ICOS, CD38 and PD-1.
View Article and Find Full Text PDFObjectives: SARS-CoV-2 can be transmitted by aerosols, and the ocular surface may be an important route of transmission. Little is known about protective antibody responses to SARS-CoV-2 in tears after infection or vaccination. We analysed the SARS-CoV-2-specific IgG and IgA responses in human tears after either COVID-19 infection or vaccination.
View Article and Find Full Text PDFThe durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection.
View Article and Find Full Text PDFThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has dramatically expedited global vaccine development efforts, most targeting the viral 'spike' glycoprotein (S). S localizes on the virion surface and mediates recognition of cellular receptor angiotensin-converting enzyme 2 (ACE2). Eliciting neutralizing antibodies that block S-ACE2 interaction, or indirectly prevent membrane fusion, constitute an attractive modality for vaccine-elicited protection.
View Article and Find Full Text PDFAim: To characterize anterior eye health and tear film characteristics in individuals with human immunodeficiency virus (HIV) undergoing anti-retroviral therapy.
Methods: This cross-sectional study involved 35 adults, categorized as healthy controls (n = 18) or as HIV-positive patients (n = 17), with no history of opportunistic infection or current ocular fundus abnormalities. Participants underwent a comprehensive anterior eye assessment.
Objective: To determine the herpes simplex virus 2 (HSV-2) seroprevalence rate in a Melbourne antenatal cohort.
Design: Prospective collection of serum and questionnaires in 1371 women attending an outpatient antenatal clinic.
Setting: A tertiary obstetric hospital in metropolitan Melbourne.