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Old 02-14-2020, 06:54 PM   #101
Hmm, so it sounds like being "recovered" from this coronavirus has a drawback:

TAIPEI (Taiwan News) — It’s possible to get infected by the novel coronavirus (COVID-19) a second time, according to doctors on the frontline in China’s city of Wuhan, leading to death from heart failure in some cases.


Now isn't that just ducky?
Old 02-15-2020, 01:19 AM   #102
Well, this is kind of technical, and honestly I can't follow all of it. But if you can follow some of it, I think it may just scare the crap out of you in it's implications.
Old 02-15-2020, 02:53 AM   #103

2019-nCoV is the virus.
COVID-19 is the disease.
Old 02-15-2020, 07:58 PM   #104
And another perspective that is just as interesting...
Old 02-16-2020, 01:43 AM   #105
Well, I am leaning more and more towards thinking this was an accidental release from the BSL-4 Lab in Wuhan, China. IMHO, they were working on a vaccine for SARS, modified the subject virus so that it would last longer in the test subjects by inhibiting the immune response, and in so doing made themselves a Frankenstein. And it escaped.

The following article was written in 2005, I believe. Sort of a premonition in parts.

SARS Vaccine Development

Shibo Jiang,corresponding author* Yuxian He,* and Shuwen Liu*

*New York Blood Center, New York, New York, USA
corresponding authorCorresponding author.
Address for correspondence: Shibo Jiang, Lindsley F. Kimball Research Institute, New York Blood Center, 310 East 67th St, New York, NY 10021, USA; fax: 212-570-3099; email: gro.retnecdoolBYN@gnaiJS

Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)–associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.

Keywords: SARS, SARS-CoV, spike protein, receptor-binding domain, Neutralizing epitone, vaccine


Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease caused by SARS-associated coronavirus (SARS-CoV) (1). It originated in the Guangdong province of China in late 2002, spread rapidly around the world along international air-travel routes, and resulted in 8,450 cases and 810 deaths in 33 countries and areas on 5 continents ( The global outbreak of SARS seriously threatened public health and socioeconomic stability worldwide. Although this outbreak was eventually brought under control in 2003, several isolated outbreaks of SARS subsequently occurred because of accidental releases of the SARS-CoV isolates from laboratories in Taiwan, Singapore, and mainland China ( In late 2003 and early 2004, new infections in persons who had contact with animals infected with SARS-CoV strains significantly different from those predominating in the 2002–2003 outbreak were reported in Guangdong, China (1). These events indicate that a SARS epidemic may recur at any time in the future, either by the virus escaping from laboratory samples or by SARS-CoV isolates evolving from SARS-CoV–like virus in animal hosts.

Origin and Evolution of SARS-CoV
Coronaviruses of the genus Coronavirus can be divided into 3 antigenic groups. Group 1 consists of human coronavirus 229E (HCoV-229E), porcine epidemic diarrhea virus, and feline infectious peritonitis virus (FIPV). Group 2 includes bovine coronavirus, murine hepatitis virus, and human coronavirus OC34 (HCoV-OC43). Group 3 contains avian infectious bronchitis virus. SARS-CoV is a new member of the genus Coronavirus, but it does not belong to any of the 3 antigenic groups, although some reports suggest that it most resembles the group 2 coronavirus (2). SARS-CoV may have originated in animals. SARS-CoV–like virus with >99% nucleotide homology with human SARS-CoV was identified in palm civets and other animals found in live animal markets in Guangdong, China (3). The SARS-CoV–like virus that exists in animals does not cause typical SARS-like disease in the natural hosts and is not transmitted from animals to humans. Under certain conditions, the virus may have evolved into the early human SARS-CoV, with the ability to be transmitted from animals to humans or even from humans to humans, resulting in localized outbreaks and mild human disease. Under selective pressure in humans, the early human SARS-CoV may further evolve into the late human SARS-CoV, which can cause local or even global outbreaks and typical SARS in humans with high death rates. Early human SARS-CoV is closer genetically to animal SARS-CoV–like virus than to late human SARS-CoV, which has a 29-nucleotide (in some isolates a 415-nucleotide) deletion in open reading frame 8 (3,4). The characteristics of these viruses are summarized in the Table (4–6).

**Table excluded**

SARS-CoV can be efficiently grown in cell culture (1) and rapidly spread from person to person (7). It can survive in feces and urine at room temperature for >2 days ( and may cause serious, even fatal, disease. SARS-CoV, a National Institute of Allergy and Infectious Diseases Biodefense Category C priority pathogen ( could be used by bioterrorists as a biological weapon. Therefore, development of effective and safe vaccines is urgently needed to prevent a new SARS epidemic and for biodefense preparedness. Currently, 3 major classes of SARS vaccines are under development: 1) inactivated SARS-CoV (Figure 1), 2) full-length S protein (Figure 2A), and 3) those based on fragments containing neutralizing epitopes (Figure 2B).

Inactivated SARS-CoV–based Vaccines
SARS-CoV expresses several structural proteins, including nucleocapsid, membrane, envelope, and spike (S) proteins (1). All may serve as antigens to induce neutralizing antibodies and protective responses. In general, prior to identification of the protein that contains the major neutralizing epitopes, the inactivated virus may be used as the first-generation vaccine because it is easy to generate whole killed virus particles. However, once the neutralizing epitopes are identified, the inactivated virus vaccine should be replaced by vaccines based on fragments containing neutralizing epitopes since they are safer and more effective. Several reports have showed that SARS-CoV inactivated with formaldehyde, UV light, and β-propiolactone can induce virus-neutralizing antibodies in immunized animals (8–11), and the first inactivated SARS-CoV vaccine is being tested in the clinical trials in China. However, safety of the inactivated vaccine is a serious concern; production workers are at risk for infection during handling of concentrated live SARS-CoV, incomplete virus inactivation may cause SARS outbreaks among the vaccinated populations, and some viral proteins may induce harmful immune or inflammatory responses, even causing SARS-like diseases (12,13).

S Protein–based Vaccines
The S protein of SARS-CoV, a type I transmembrane glycoprotein, is responsible for virus binding, fusion, and entry and is a major inducer of neutralizing antibodies (1,14). S protein consists of a signal peptide (SP: amino acids [aa] 1–12) and 3 domains: an extracellular domain (aa 13–1193), a transmembrane domain (aa 11194–1215), and an intracellular domain (aa 1216–1255). Its extracellular domain consists of 2 subunits, S1 and S2 (14), although the cleavage site between these subunits has not been clearly defined. The S1 subunit is responsible for virus binding to the receptor, angiotensin-converting enzyme 2 (ACE2) (15,16). A fragment located in the middle region of the S1 subunit (aa 318–510) is the receptor-binding domain (RBD) for ACE2 (17–19). SARS-CoV may also bind to cells through the alternative receptors DC-SIGN or L-SIGN (20,21), but the binding sites for these alternative receptors have not been defined. The S2 subunit, which contains a putative fusion peptide and 2 heptad repeats (HR1 and HR2), is responsible for fusion between the viral and target cell membranes. Infection by SARS-CoV is initiated by binding of RBD in the viral S protein S1 subunit to ACE2 on target cells. This forms a fusogenic core between the HR1 and HR2 regions in the S2 domain that brings the viral and target cell membranes into close proximity, which results in virus fusion and entry (22–24). This scenario indicates that the S protein may be used as a vaccine to induce antibodies for blocking virus binding and fusion.

Several recombinant vector-based vaccines expressing SARS-CoV S protein have been assessed in preclinical studies. Yang et al. (25) reported that a candidate DNA vaccine encoding the full-length S protein induced neutralizing antibodies (neutralizing titers ranging from 1:50 to 1:150) and protected mice from SARS-CoV challenge. Using DNA vaccines encoding the full-length and segments of S protein to immunize rabbits, Wang et al. have produced higher titers of neutralizing antibodies and demonstrated that major and minor neutralizing epitopes are located in the S1 and S2 subunits, respectively (26). Other groups also found neutralizing epitopes in the S2 subunit (27,28). Bisht et al. (29) have shown that intranasal or intramuscular inoculations of mice with highly attenuated modified vaccinia virus Ankara (MVA) vaccines encoding full-length SARS-CoV S protein also produce neutralizing antibodies with mean neutralizing titers of 1:284. Bukreyev et al. (30) reported that mucosal immunization of African green monkeys with an attenuated parainfluenza virus expressing S protein resulted in production of neutralizing antibodies and protected animals from infection by challenge with SARS-CoV. These data suggest that the S protein can induce neutralizing antibodies and protective responses in immunized animals.

Using convalescent-phase sera from SARS patients and a set of peptides spanning the entire sequence of the SARS-CoV S protein, we have identified 5 linear immunodominant sites (IDS) in the S protein (Figure 2A). IDS I, II, III, and V reacted with >50% of the convalescent-phase sera from SARS patients, while IDS IV was reactive with >80% of SARS sera, suggesting that IDS IV is the major immunodominant epitope on the S protein (31). Synthetic peptides corresponding to IDS could induce high titers of S protein–specific antibodies, but none of these antibodies possesses neutralizing activity. These findings suggest that the IDS in S protein may not induce neutralizing antibodies. Whether these antibodies enhance infection by heterologous SARS-CoV strains or mediate harmful immune responses is unclear. The S protein of FIPV expressed by recombinant vaccinia can cause antibody-dependent enhancement of disease if vaccinated animals are subsequently infected with wild-type virus (32). Our previous studies on HIV-1 showed that antibodies against some immunodominant epitopes in the HIV-1 envelope glycoprotein could enhance infection by heterologous HIV-1 strains (33). Most recently, Yang et al. (6) demonstrated that the polyclonal and monoclonal antibodies against S protein of the late SARS-CoV (Urbani strain) could neutralize infection by the relevant late SARS-CoV strains. However, these antibodies enhanced infection by an early human SARS-CoV isolate (GD03T0013) and the civet SARS-CoV–like viruses. These investigators have shown that the ACE2-binding domain mediates the antibody-dependent enhancement of civet SARS-CoV–like virus entry (6). Theoretically, some antibodies to the ACE2-binding domain may enhance infection if these antibodies closely mimic the receptor ACE2 and induce similar conformational changes, as the receptor likely does. The S protein with truncation at aa 1153 failed to cause antibody-dependent enhancement of infection, although it still induced neutralizing antibodies. This finding suggests that removal of the aa 1153–1194 region may abrogate induction of virus infection–enhancing antibodies (6). Vaccination of ferrets with MVA-based SARS vaccine expressing full-length S protein caused liver damage after animals were challenged with SARS-CoV (34). These findings raised concerns about the efficacy and safety of the vaccines containing or expressing full-length S protein.

Vaccines Based on Fragments Containing Neutralizing Epitopes
RBD, a fragment (≈193 aa residues) in the middle of S1 subunit of S protein (Figure 2B), is responsible for virus binding to the receptor on target cells. We have demonstrated that the antisera from SARS patients and from animals immunized with inactivated SARS-CoV reacted strongly with RBD (9,35). Absorption of antibodies by RBD from these antisera results in the removal of most of the neutralizing antibodies, and RBD-specific antibodies isolated from these antisera have potent neutralizing activity (35,36). We have also shown that rabbits and mice immunized with RBD produced high titers of neutralizing antibodies against SARS-CoV with 50% neutralizing titers at a >1:10,000 serum dilution (37). The immunized mice were protected from SARS-CoV challenge (unpub. data). The antibodies purified from the antisera against SARS-CoV significantly inhibited RBD binding to ACE2 (9,36–38). Using spleen cells from mice immunized with RBD, we have generated a panel of 25 monoclonal antibodies (MAbs) that recognize different conformational epitopes on RBD and possess potent neutralizing activity (38). Our result is in agreement with the report by van den Brink et al. (39), who identified 3 human neutralizing anti-S MAbs from antibody phage display libraries by using inactivated SARS-CoV as the target. These researchers also found that all of these MAbs specifically bound to RBD and blocked interaction between RBD and ACE2. These findings suggest that RBD contains the major neutralizing epitopes in the S protein and is an ideal SARS vaccine candidate because RBD contains the receptor-binding site, which is critical for virus attachment to the target cell for infection (15,17–19). Antibodies specific for RBD are expected to block binding of virus to the target cell. RBD induces higher titers of neutralizing antibodies than those vaccines expressing the full-length S protein (25,26,29,30,37,38). RBD sequences among the late SARS-CoV strains are highly conserved. When the early and late SARS-CoV strains are compared, only 3 to 5 aa residues are variable among the 193 residues in RBD and most of the isolates vary by only 1 residue (4). van den Brink et al. (39) showed that 1 human MAb (CR3014) specific for RBD of SARS-CoV strain FM1 can effectively bind to most RBDs of the early and late SARS-CoV strains. These data suggest that antibodies directed against RBD of a SARS-CoV isolate may neutralize infection by a broad spectrum of SARS-CoV strains. Therefore, recombinant proteins containing RBD or vectors encoding RBD may be used as vaccines for preventing infection by SARS-CoV with distinct genotypes.

An ideal SARS vaccine should 1) elicit highly potent neutralizing antibody responses against a broad spectrum of viral strains; 2) induce protection against infection and transmission; and 3) be safe by not inducing any infection-enhancing antibodies or harmful immune or inflammatory responses. Currently, an inactivated SARS-CoV vaccine is in clinical trials in China. Safety is the major concern for this type of vaccine (12). The S protein is the major inducer of neutralizing antibodies. Recombinant vector-based vaccines expressing full-length S protein of the late SARS-CoV are under development. These vaccines can induce potent neutralizing and protective responses in immunized animals but may induce antibodies that enhance infection by early human SARS-CoV and animal SARS-CoV–like viruses (6). Recent studies have demonstrated that recombinant RBD consists of multiple conformational neutralizing epitopes that induce highly potent neutralizing antibodies against SARS-CoV (9,26,35–38). Unlike full-length S protein, RBD does not contain immunodominant sites that induce nonneutralizing antibodies. RBD sequences are relatively conserved. Thus, recombinant RBD or vectors encoding RBD may be used as safe and efficacious vaccines for preventing infection by SARS-CoV with distinct genotypes.

Dr. Jiang is associate member and head of the Viral Immunology Laboratory, Lindsley F. Kimball Research Institute, New York Blood Center. His primary research interests include development of vaccines and therapeutic agents against SARS-CoV and HIV.

Suggested citation for this article: Jiang S, He Y, Liu S. SARS vaccine development. Emerg Infect Dis [serial on the Internet]. 2005 Jul [date cited].

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Old 02-16-2020, 02:35 AM   #106
Not good news at all.........
Old 02-16-2020, 08:41 AM   #107
Not good:

The New York Times

After hundreds of passengers were allowed to disembark from a cruise ship in Cambodia, an American tested positive for coronavirus.
Sunday, February 16, 2020 4:12 AM EST
Officials said that more than 140 other passengers had flown to Kuala Lumpur and that most had been allowed to continue to destinations in the United States, the Netherlands and Australia.
Old 02-16-2020, 12:57 PM   #108
I do hope there is a very good reason why most governments are not taking this seriously. I would like to think they have the resources to know more about this than I do, because from what I can see, well, let's just say that I find this worrisome.

I sure do hope it winds up that there was really nothing to worry about at all.
Old 02-16-2020, 03:19 PM   #109

China: Vaccine Law Passed

(Aug. 27, 2019) On June 29, 2019, the National People’s Congress Standing Committee of the People’s Republic of China (PRC or China) adopted the PRC Law on Vaccine Administration (Vaccine Law). The official Xinhua news agency states that the Law provides for the “strictest” vaccine management with tough penalties in order to ensure the country’s vaccine safety.

Before the passage of this 100-article Law, provisions governing vaccines were contained in the PRC Drug Administration Law, PRC Law on the Prevention and Treatment of Infectious Diseases, and a few relevant administrative regulations and rules.

The new Law provides for regulatory requirements for researching, producing, distributing, and using vaccines. Such requirements, according to one legal commentator, are much more stringent than those for other drugs (art. 2). It also contains a chapter specifying penalties for violating the Vaccine Law, which are also stricter than those for violating other drug laws (ch. 10). According to the Law, if any violation of this Law constitutes a crime, a “heavier punishment” within the range of punishments provided by the Criminal Law on the relevant crimes is to be imposed (art. 79).

The Law mandates the launching of a national vaccine electronic tracking platform that integrates tracking information throughout the whole process of vaccine production, distribution, and use to ensure all vaccine products can be tracked and verified (art. 10).

According to the Law, China is to implement a state immunization program, and residents living within the territory of China are legally obligated to be vaccinated with immunization program vaccines, which are provided by the government free of charge. Local governments and parents or other guardians of children must ensure that children be vaccinated with the immunization program vaccines (art. 6).

The Law establishes a compensation system for abnormal reactions to vaccination. A recipient of an immunization program vaccine who dies or suffers significant disability or organ and tissue damage is to be paid from the vaccination funds of the provincial level government if the damage falls within the scope of abnormal reactions associated with a vaccine or cannot be prevented (art. 56).

The Law will take effect on December 1, 2019 (art. 100).

Author: Laney Zhang
Topic: Drug safety, Health promotion and preventive care, Public health
Jurisdiction: China
Date: August 27, 2019


Which, coincidentally enough seems to be when some sources believe this 2019-nCoV virus first gained a toehold in China.
Old 02-22-2020, 08:18 PM   #110
Things aren't looking good.

Chinese Coronavirus Patient Reinfected 10 Days After Leaving Hospital

by Tyler Durden
Fri, 02/21/2020 - 13:05

As we first reported on Monday, shortly after the US decided to break the quarantine surrounding the Diamond Princess cruise ship which had emerged as the single-biggest locus of coronavirus cases outside of China, hundreds of weary, homesick Americans were on their way home. And as more than a dozen buses sat on the tarmac at Tokyo’s Haneda Airport with 328 Americans wearing surgical masks and gloves inside, awaiting anxiously to fly home after weeks in quarantine aboard the Diamond Princess, U.S. officials wrestled with troubling news: new test results showed that 14 passengers were infected with the virus. The problem: the U.S. State Department had promised that no one with the infection would be allowed to board the planes.

A decision had to be made. Let them all fly? Or leave them behind in Japanese hospitals? At this point, according to the Washington Post, a fierce debate broke out in Washington, where it was still Sunday afternoon: The State Department and a top Trump administration health official wanted to forge ahead. The infected passengers had no symptoms and could be segregated on the plane in a plastic-lined enclosure (something we mocked on Monday when we said "we can only hope that "plastic divider" was enough to keep the virus confined to its own class aboard the aircraft."). At this point, officials at the Centers for Disease Control and Prevention disagreed, contending they could still spread the virus. The CDC believed the 14 should not be flown back with uninfected passengers.

"It was like the worst nightmare,” said a senior U.S. official involved in the decision, speaking on the condition of anonymity to describe private conversations. “Quite frankly, the alternative could have been pulling grandma out in the pouring rain, and that would have been bad, too."

In the end, the State Department won the argument. But unhappy CDC officials demanded to be left out of the news release that explained that infected people were being flown back to the United States — a move that would nearly double the number of known coronavirus cases in this country.

In retrospect, the CDC will soon be proven correct in its dire warning that repatriating a full plane of both infected and healthy individuals could be a catastrophic error, because it now appears that not only can the virus remain latent for as long as 42 days, 4 weeks longer than traditionally assumed, resulting in numerous false negative cases as infected carrier slip across borders undetected, but far more ominously, it now appears that the diseases can re-infect recently "cured" patients, because as Taiwan News reports, a Chinese patient who just recovered from the Wuhan coronavirus (COVID-19) has been infected for the second time in the province of Sichuan, according to local health officials.

On Wednesday (Feb. 19), the People's Daily reported that a man in Sichuan's capital Chengdu had tested positive for the virus during a regular check-up just ten days after being discharged from the hospital. The report said he had previously been cleared of the virus by medical staff.

The Sichuan Health Commission confirmed the news on Friday (Feb. 21) and issued a community warning announcement in the patient's neighborhood. The announcement said that the man and his family had been transported to a nearby health facility on Thursday morning (Feb. 20) and that health officials had sanitized the entire community, reported Liberty Times.

According to ETtoday, the patient and his family had been under home quarantine and had not left the house since Feb. 10. The authorities are still investigating the cause of the reinfection.

The news has stirred up heated reactions from Chinese netizens. Some suspect that the hospital discharged the man before he was fully recovered, and many have expressed concern about the worsening epidemic.

Several doctors from Wuhan, the epicenter of COVID-19, said last week that it is possible for recovered patients to contract the virus a second time. They warned that a recurring infection could be even more damaging to a patient's body and that the tests are susceptible to false negatives.

Needless to say, with the US now repatriating over a dozen coronavirus-infected individuals, it will be absolutely critical to keep a close eye on any deemed healthy or cured, because it now appears that not only can the virus stay latent for nearly a month longer than previously expected, but cured patients can also get reinfected.

And all of this is probably why, in a far more gloomier sounding press conference, today the CDC warned that:


In short, it's only a matter of time before the pandemic, which is already "contained" in nearly 30 cases in the US as of this moment, becomes uncontained, and the exponential chart of cases away from China, includes the US in it.

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