The highly conserved M2 proton channel was proposed as a potential target for broadly neutralizing antibodies.The challenges for researchers are to identify single antibodies that could neutralize many subtypes of the virus, so that they could be useful in any season, and that target conserved domains that are resistant to antigenic drift.Another approach is to take the conserved domains identified from these projects, and to deliver groups of these antigens to provoke an immune response; various approaches with different antigens, presented different ways (as fusion proteins, mounted on virus-like particles, on non-pathogenic viruses, as DNA, and others), are under development.Efforts have also been undertaken to develop universal vaccines that specifically activate a T-cell response, based on clinical data showing that people with a strong, early T-cell response have better outcomes when infected with influenza and because T-cells respond to conserved epitopes. The challenge for developers is that these epitopes are on internal protein domains that are only mildly immunogenic.Along with the rest of the vaccine field, people working on universal vaccines have experimented with vaccine adjuvants to improve the ability of their vaccines to create a sufficiently powerful and enduring immune response. Oral influenza vaccine
As of 2019, an oral flu vaccine was in clinical research. The oral vaccine candidate is based on an adenovirus type 5 vector modified to remove genes needed for replication, with an added gene that expresses a small double-stranded RNA hairpin molecule as an adjuvant.
The hypothesis of autosomal recessive inheritance of Vici syndrome was strengthened in 2002 with the clinical description of two new cases, one brother and one sister, by Chiyonobu et al. Gene
Vici syndrome is caused by mutations in the gene EPG5 (OMIM # 615068), which encodes an important regulator of the autophagy pathway, the ectopic P-granules autophagy protein 5, involved in the formation of lysosomes. EPG5 is the human homolog of the C.elegans epg5 gene. The gene EPG5 has been cloned for the first time by Nagase et al. by sequencing clones obtained from a size-fractionated fetal brain cDNA library, and was initially named KIAA1632.The EPG5 human gene is located on chromosome 18q12.3, has a length of 119,67Kb (NC_000018.10), consists of 44 exons and is transcriptionally driven from the centromere toward the telomere. The messenger RNA (mRNA) is 12633bp long (NM_020964.2) and contains a CDS of 7740 bp translated into a protein sequence of 2579 amino acids (NP_066015.2) with a molecular weight of 280kDa, presumed. The protein EPG5 is expressed primarily in the central nervous system (CNS), skeletal muscle, heart, thymus, cells of the immune system, lungs and kidneys.Mutations in the EPG5 gene interfere with the autophagy. This appears to be due to a block in the autophagosome-lysosome fusion mechanism. Diagnosis
The diagnostic workup usually includes an MRI of the brain, an EEG, ophthalmic examination and a cardiac ECHO. Muscle biopsy – which is not commonly done – may show storage of abnormal material and secondary mitochondrial abnormalities in skeletal muscle.