抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years. The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.

/pdf/sars-cov-2-vaccines-in-development-31fwfnvrk5.pdf

SARS-CoV-2 vaccines in development.

A total of 4 of 107 persons (4%) who were born after 1980 had preexisting crossreactive antibody titers of 40 or more against 2009 H1N1, whereas 39 of 115 persons (34%) born before 1950 had titers of 80 or more. Vaccination with seasonal trivalent inactivated influenza vaccines resulted in an increase in the level of crossreactive antibody to 2009 H1N1 by a factor of four or more in none of 55 children between the ages of 6 months and 9 years, in 12 to 22% of 231 adults between the ages of 18 and 64 years, and in 5% or less of 113 adults 60 years of age or older. Seasonal vaccines that were formulated with adjuvant did not further enhance cross-reactive antibody responses. Vaccination with the A/New Jersey/1976 swine influenza vaccine substantially boosted cross-reactive antibodies to 2009 H1N1 in adults.

/pdf/cross-reactive-antibody-responses-to-the-2009-pandemic-h1n1-b13eye709v.pdf

Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus

A highly pathogenic avian influenza virus, H5N1, caused disease outbreaks in poultry in China and seven other east Asian countries between late 2003 and early 2004; the same virus was fatal to humans in Thailand and Vietnam. Here we demonstrate a series of genetic reassortment events traceable to the precursor of the H5N1 viruses that caused the initial human outbreak in Hong Kong in 1997 (refs 2-4) and subsequent avian outbreaks in 2001 and 2002 (refs 5, 6). These events gave rise to a dominant H5N1 genotype (Z) in chickens and ducks that was responsible for the regional outbreak in 2003-04. Our findings indicate that domestic ducks in southern China had a central role in the generation and maintenance of this virus, and that wild birds may have contributed to the increasingly wide spread of the virus in Asia. Our results suggest that H5N1 viruses with pandemic potential have become endemic in the region and are not easily eradicable. These developments pose a threat to public and veterinary health in the region and potentially the world, and suggest that long-term control measures are required.

Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. The viral haemagglutinin (HA) protein is a known host-range determinant as it mediates virus binding to hostspecific cellular receptors 1–3 . Here we assess the molecular changes in HA that would allow a virus possessing subtype H5 HA to be transmissible among mammals. We identified a reassortant H5 HA/H1N1 virus—comprising H5 HA (from an H5N1 virus) with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus—that was capable of droplet transmission in a ferret model. The transmissible H5 reassortant virus preferentially recognized human-type receptors, replicated efficiently in ferrets, caused lung lesions and weight loss, but was not highly pathogenic and did not cause mortality. These results indicate that H5 HA can convert to an HA that supports efficient viral transmission in mammals; however, we do not know whether the four mutations in the H5 HA identified here would render a wholly avian H5N1 virus transmissible. The genetic origin of the remaining seven viral gene segments may also critically contribute to transmissibility in mammals. Nevertheless, as H5N1 viruses continue to evolve and infect humans, receptor-binding variants of H5N1 viruses with pandemic potential, including avian–human reassortant viruses as tested here, may emerge. Our findings emphasize the need to prepare for potential pandemics caused by influenza viruses possessing H5 HA, and will help individuals conducting surveillance in regions with circulating H5N1 viruses to

/pdf/experimental-adaptation-of-an-influenza-h5-ha-confers-3gi1a06ra1.pdf

Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets

http://www.ijidonline.com/article/S1201971223000474/pdf

Kiyoko Iwatsuki-Horimoto

Papers

High titers of infectious SARS-CoV-2 in corpses of patients with COVID-19