Ho, J. K. | Search bioRxiv

bioRxiv2023

mRNA vaccines encoding membrane-anchored receptor-binding domains of SARS-CoV-2 mutants induce strong humoral responses and can overcome immune imprinting

To address the limitations of whole-spike COVID vaccines, we explored mRNA vaccines encoding membrane-anchored receptor-binding domain (RBD-TMs), each a fusion of a variant RBD, the transmembrane (TM) and cytoplasmic tail (CT) fragments of the SARS-CoV-2 spike protein. In naive mice, RBD-TM mRNA vaccines against ancestral SARS-CoV-2, Beta, Delta, Delta-plus, Kappa, Omicron BA.1 or BA.5, all induced strong humoral responses against the target RBD. Multiplex surrogate viral neutralization (sVNT) assays indicated broad neutralizing activity against a range of variant RBDs. In the setting of a heterologous boost, against the background of exposure to ancestral whole spike vaccines, sVNT studies suggested that RBD-TM vaccines were able to overcome the detrimental effects of immune imprinting. Omicron BA.1 and BA.5 RBD-TM booster vaccines induced serum antibodies with 12 and 22-fold higher neutralizing activity against the target RBD than their equivalent whole spike variants. Boosting with BA.1 or BA.5 RBD-TM provided good protection against more recent variants including XBB and XBB.1.5. Each RBD-TM mRNA is 28% of the length of its whole-spike equivalent. This advantage will enable tetravalent mRNA vaccines to be developed at well-tolerated doses of formulated mRNA. One Sentence SummarymRNA vaccines encoding membrane-anchored RBDs of SARS-CoV-2 mutants are effective vaccines that can overcome immune imprinting in mice

immunology↗

bioRxiv2022

Inter-individual deep image reconstruction

The sensory cortex is characterized by general organizational principles such as topography and hierarchy. However, measured brain activity given identical input exhibits substantially different patterns across individuals. Although anatomical and functional alignment methods have been proposed in functional magnetic resonance imaging (fMRI) studies, it remains unclear whether and how hierarchical and fine-grained representations can be converted between individuals while preserving the encoded perceptual content. In this study, we trained a method of functional alignment called neural code converter that predicts a target subjects brain activity pattern from a source subject given the same stimulus, and analyzed the converted patterns by decoding hierarchical visual features and reconstructing perceived images. The converters were trained on fMRI responses to identical sets of natural images presented to pairs of individuals, using the voxels on the visual cortex that covers from V1 through the ventral object areas without explicit labels of the visual areas. We decoded the converted brain activity patterns into the hierarchical visual features of a deep neural network using decoders pre-trained on the target subject and then reconstructed images via the decoded features. Without explicit information about the visual cortical hierarchy, the converters automatically learned the correspondence between visual areas of the same levels. Deep neural network feature decoding at each layer showed higher decoding accuracies from corresponding levels of visual areas, indicating that hierarchical representations were preserved after conversion. The visual images were reconstructed with recognizable silhouettes of objects even with relatively small numbers of data for converter training. The decoders trained on pooled data from multiple individuals through conversions lead to a slight improvement over those trained on a single individual. These results demonstrate that the hierarchical and fine-grained representation can be converted by functional alignment, while preserving sufficient visual information to enable inter-individual visual image reconstruction. Highlights[bullet] Neural code converters convert brain activity patterns across individuals with moderate conversion accuracy and learn reasonable visual area correspondences at the same level between individuals. [bullet]The converted brain activity patterns can be decoded into hierarchical DNN features to reconstruct visual images, even though the converter is trained on a small number of data samples. [bullet]The information of hierarchical and fine-scale visual features that enable visual image reconstruction are preserved after functional alignment.

neuroscience↗