ABSTRACT
Influenza epidemics and pandemics caused by newly emerging virus strains highlight an urgent need to develop a universal vaccine against viruses. Previously, a monoglycosylated X-181mg vaccine demonstrated that the HA possessing a single N-acetylglucosamine at each N-glycosylation site is superior to confer broader protection in mice than conventional vaccines. However, the greatest challenge in conducting clinical trials is the need to develop robust manufacturing processes capable of producing vaccines at the pilot scale with the desired stability, potency, and efficacy. Whether the monoglycosylated virus vaccine platform can be applied to the new vaccine strain in a timely manner and whether the mass-produced vaccine has the proper immunogenicity to induce cross-protective immunity remains unclear. Here, we show that a pilot-scale manufacturing process produced a monoglycosylated A/Brisbane/02/2018(H1N1) virus vaccine (IVR-190mg) with a single glycan at each glycosylation site of HA and NA. Compared with the fully glycosylated virus vaccine (IVR-190fg), the IVR-190mg provided broader cross-protection in mice against a wide range of H1N1 variants. The enhanced antibody responses induced by IVR-190mg immunization include higher hemagglutination-inhibition titers, higher neutralization activity, more anti-HA head domain, more anti-HA stem antibodies, higher neuraminidase activity inhibition titers, and notably, higher antibody-dependent cellular cytotoxicity. Additionally, the IVR-190mg also induced a more balanced Th1/Th2 response and elicited broader splenic CD4+ and CD8+ T-cell responses than IVR-190fg. This study demonstrated that IVR-190mg produced using a pilot-scale manufacturing process elicits comprehensive cross-strain immune responses that have great potential to substantially mitigate the need for yearly reformulation of strain-specific inactivated vaccines.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Orthomyxoviridae Infections , Animals , Mice , Humans , Antibodies, Viral , Vaccines, Inactivated , Hemagglutinin Glycoproteins, Influenza VirusABSTRACT
This paper presents a capacitorless low-dropout (LDO) regulator with fast transient response and data reverse telemetry circuit for fully implantable wireless transmission applications. We propose a novel hybrid feedback structure using high-frequency compensation technology to achieve a rapid transient response for the LDO regulator. To reduce the size of the implant and transmit neural recordings through the same coil without interfering with power transmission, the load-shift-key (LSK) modulation technique is adopted for back data telemetry. The proposed implantable chip, fabricated using commercial 0.18 µm complementary metal oxide semiconductor technology, yielded an output power of 15 mW. Under 1.15 V operation voltage, the maximum overshoot and undershoot voltages were less than 45 mV and 55 mV, respectively, for a 15 mA full-load current whose rising and falling time were less than 100 ns. The proposed LSK transceiver uses a digitized demodulator to improve bandwidth efficiency for low carrier frequency operation.
Subject(s)
Prostheses and Implants , Telemetry/instrumentation , Wireless Technology/instrumentation , Electric Power Supplies , Equipment Design , Humans , Signal Processing, Computer-AssistedABSTRACT
Although deep brain stimulation (DBS) has been a promising alternative for treating several neural disorders, the mechanisms underlying the DBS remain not fully understood. As rat models provide the advantage of recording and stimulating different disease-related regions simultaneously, this paper proposes a battery-less, implantable neuro-electronic interface suitable for studying DBS mechanisms with a freely-moving rat. The neuro-electronic interface mainly consists of a microsystem able to interact with eight different brain regions bi-directionally and simultaneously. To minimize the size of the implant, the microsystem receives power and transmits data through a single coil. In addition, particular attention is paid to the capability of recording neural activities right after each stimulation, so as to acquire information on how stimulations modulate neural activities. The microsystem has been fabricated with the standard 0.18 µm CMOS technology. The chip area is 7.74 mm (2) , and the microsystem is able to operate with a single supply voltage of 1 V. The wireless interface allows a maximum power of 10 mW to be transmitted together with either uplink or downlink data at a rate of 2 Mbps or 100 kbps, respectively. The input referred noise of recording amplifiers is 1.16 µVrms, and the stimulation voltage is tunable from 1.5 V to 4.5 V with 5-bit resolution. After the electrical functionality of the microsystem is tested, the capability of the microsystem to interface with rat brain is further examined and compared with conventional instruments. All experimental results are presented and discussed in this paper.