Live vaccine infection burden elicits adaptive humoral and cellular immunity required to prevent Zika virus infection

10.1016/j.ebiom.2020.103028EBioMedicine6110302

Viruses engage inhibitory receptors to down-regulate antiviral responses.

<p>Viruses engage inhibitory receptors to down-regulate antiviral responses.</p

Viral manipulation of inhibitory signaling drives chronic and persistent infections.

<p>Viral manipulation of inhibitory signaling drives chronic and persistent infections.</p

Viral evasion of NK cell-mediated immunity.

<p>Viral evasion of NK cell-mediated immunity.</p

An experimental medicine decipher of a minimum correlate of cellular immunity: Study protocol for a double-blind randomized controlled trial

10.3389/fimmu.2023.1135979FRONTIERS IN IMMUNOLOGY1

Genomic signature of early T-cell response is associated with lower antibody titer threshold for sterilizing immunity

Vaccination is an effective approach to reduce disease burden. High vaccination coverage blocks pathogen transmission to ensure herd immunity. However, the concept of herd immunity assumes that vaccinated individuals cannot be infected and mediate silent pathogen transmission. While the correlates of vaccine-mediated protection against disease have been examined, the correlates of sterilizing immunity that prevents infection have not been systematically defined. Here, we used full genome expression profiling to explore the molecular correlates of serological response and non-response to measles, mumps and rubella (MMR) vaccination as surrogates of infection and sterilizing immunity, respectively. We observed that the antibody titers needed to sterilize infection with the vaccine strains were higher than current WHO disease protection thresholds. In subjects with baseline antibodies below such sterilizing immunity thresholds, serological non-response to MMR vaccination was associated with gene expression profile indicative of early T-cell activation and signalling. Specifically, genes that regulate T-cell function and response were induced at day 1 post-vaccination in non-responders but not in responders. These findings suggest that rapid T-cell response prevented MMR vaccine infection to limit antigenic presentation and hence serological response. Collectively, our findings suggest an important role for T-cells in engendering sterilizing immunity.publishedVersionPeer reviewe

A fast-growing dengue virus mutant reveals a dual role of STING in response to infection

The four dengue viruses (DENVs) have evolved multiple mechanisms to ensure its survival. Among these mechanisms is the ability to regulate its replication rate, which may contribute to avoiding premature immune activation that limit infection dissemination: DENVs associated with dengue epidemics have shown slower replication rate than pre-epidemic strains. Correspondingly, wild-type DENVs replicate more slowly than their clinically attenuated derivatives. To understand how DENVs ‘make haste slowly’, we generated and screened for DENV2 mutants with accelerated replication that also induced high type-I interferon (IFN) expression in infected cells. We chanced upon a single NS2B-I114T amino acid substitution, in an otherwise highly conserved amino acid residue. Accelerated DENV2 replication damaged host DNA as mutant infection was dependent on host DNA damage repair factors, namely RAD21, EID3 and NEK5. DNA damage induced cGAS/STING signalling and activated early type-I IFN response that inhibited infection dissemination. Unexpectedly, STING activation also supported mutant DENV replication in infected cells through STING-induced autophagy. Our findings thus show that DENV NS2B has multi-faceted role in controlling DENV replication rate and immune evasion and suggest that the dual role of STING in supporting virus replication within infected cells but inhibiting infection dissemination could be particularly advantageous for live attenuated vaccine development

Temporal dynamics of the host molecular responses underlying severe COVID-19 progression and disease resolution

10.1016/j.ebiom.2021.103262EBioMedicine6510326