A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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数据之美——聚焦全球器官捐献发展趋势

器官移植术是20世纪出现的针对器官功能衰竭的最有效治疗方法，每年拯救全球超过12万例患者。但供器官短缺的现状，与器官移植技术和辅助药物的发展不匹配，制约了器官移植事业的发展。我国自2015年起已成为全球器官捐献和移植大国之一，2017年公民逝世后器官捐献数量超过5 000例，占全球捐献总量的15%以上。黄洁夫教授总结的器官捐献与移植"中国模式"得到了世界卫生组织、国际移植界的高度重视和充分肯定。本文通过整理全球及各国的器官捐献与移植数据，剖析全球现状与发展趋势，进一步探索我国公民器官捐献的影响因素并提出针对性的应对策略，以期实现我国器官捐献和移植的"自给自足"。     

Myelopathy due to human T-cell leukemia virus type-1 from the donor after ABO-incompatible liver transplantation

We report the case of a 53-year-old-man who developed human T-cell leukemia virus type-1-associated myelopathy (HAM) after ABO-incompatible liver transplantation for alcoholic liver cirrhosis. The living donor was seropositive for human T-cell leukemia virus type-1 (HTLV-1) and the recipient was seronegative for HTLV-1 before transplantation. After transplantation, the recipient developed steroid-resistant acute cellular rejection, which was successfully treated using anti-thymocyte globulin, and he was eventually discharged. He underwent spinal surgery twice after the transplantation for the treatment of cervical spondylosis that had been present for a period of 9 months before the transplantation. The surgery improved his gait impairment temporarily. However, his gait impairment progressed, and magnetic resonance imaging revealed multiple sites of myelopathy. He was diagnosed with HAM 16 months after the transplantation. Pulse steroid therapy (1000 mg) was administered over a period of 3 days, and his limb paresis improved. Presently, steroid therapy is being continued, with a plan to eventually taper the dose, and he is being carefully followed up at our institution. Our case suggests that liver transplantation involving an HTLV-1-positive living donor carries the risk of virus transmission and short-term development of HAM after transplantation.     

Heterosubtypic immunity to H7N9 influenza virus in isogenic guinea pigs after infection with pandemic H1N1 virus

Heterosubtypic immunity is defined as immune-mediated (partial) protection against an influenza virus induced by an influenza virus of another subtype to which the host has not previously been exposed. This cross-protective effect has not yet been demonstrated to the newly emerging avian influenza A viruses of the H7N9 subtype. Here, we assessed the induction of protective immunity to these viruses by infection with A(H1N1)pdm09 virus in a newly developed guinea pig model. To this end, ten female 12–16 week old strain 2 guinea pigs were inoculated intratracheally with either A(H1N1)pdm09 influenza virus or PBS (unprimed controls) followed 4 weeks later with an A/H7N9 influenza virus challenge. Nasal swabs were taken daily and animals from both groups were sacrificed on days 2 and 7 post inoculation (p.i.) with A/H7N9 virus and full necropsies were performed.Nasal virus excretion persisted until day 7 in unprimed control animals, whereas only two out of seven H1N1pdm09-primed animals excreted virus via the nose. Infectious virus was recovered from nasal turbinates, trachea and lung of all animals at day 2 p.i., but titers were lower for H1N1pdm09-primed animals, especially in the nasal turbinates. By day 7 p.i., relatively high virus titers were found in the nasal turbinates of all unprimed control animals but infectious virus was isolated from the nose of only one of four H1N1pdm09-primed animals.Animals of both groups developed inflammation of variable severity in the entire respiratory tract. Viral antigen positive cells were demonstrated in the nasal epithelium of both groups at day 2. The bronchi(oli) and alveoli of unprimed animals showed a moderate to strong positive signal at day 2, whereas H1N1pdm09-primed animals showed only minimal positivity. By day 7, only viral antigen positive cells were found after H7N9 virus infection in the nasal turbinates and the lungs of unprimed controls. Thus infection with H1N1pdm09 virus induced partially protective heterosubtypic immunity to H7N9 virus in (isogenic) guinea pigs that could not be attributed to cross-reactive virus neutralizing antibodies.