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Experimental monkey, the most critical resource in the new crown vaccine battle

 The macaque is an omnivorous animal, mainly vegetarian. Its brain structure, physiological functions and genes are similar to humans, and it has advanced cognitive behaviors.



  The new crown pneumonia epidemic has been raging around the world for more than a year, and many countries have pinned their hopes on vaccination.

  On May 3, the American Indian-born infectious disease expert Ragusa Kapila passed away in India after contracting the new crown virus, which caused widespread concern in the international world. Before going to India, Kapila had been vaccinated with two doses of Pfizer vaccine produced in the United States, but after going to India he was still infected with the new coronavirus locally and eventually died of multiple organ failure.

  Immediately afterwards, the mutated new coronavirus that was first discovered in India was listed as a mutation of concern by the World Health Organization, indicating that the mutation of this virus is worrying. This has once again aroused people's worries about the effectiveness of vaccine immunity. The good news is that the vaccine produced in China has been proven by many countries to be "very effective in the real world."

  The Brazilian town of Serana was one of the most severely affected areas in Brazil at the beginning of the epidemic. However, starting on February 19 this year, in just two months, almost all adults eligible for vaccination in the city have been vaccinated China’s Kexing Vaccine was released. On May 7, the Wall Street Journal of the United States described in detail the status quo in the small city-compared with the peak of the epidemic in March, the infection rate of Serrana dropped by 75%, and among the people who received two doses of the vaccine, it did not appear. Deaths caused by the new coronavirus. Today, in Serana, children screaming and laughing across the main square, groups of friends will stop to chat and sunbathe in the afternoon. The Wall Street Journal reported that the This experiment has brought hope to countries around the world that are still fighting the epidemic.

  In addition to rejuvenating the small towns of Brazil, the new crown vaccine has also shown good results among vaccinators in Indonesia.

  On May 11, Indonesian Minister of Health Sadikin stated in an interview that the country followed up the situation of 25,374 medical workers in Jakarta who received the second dose of Coxing vaccine for 28 days. The results showed that seven days after the completion of the vaccination , Kexing vaccine can protect 100% of vaccinators from death (due to new coronary pneumonia) and 96% of vaccinators from hospitalization (due to new coronary pneumonia).

  Sadikin also added that 94% of medical workers were protected from infection after being vaccinated with Kexing vaccine. This result is very impressive. The actual application effect of Kexing vaccine is better than its results in multiple clinical trials. He said: “We have seen a very, very sharp decline in the number of hospitalizations and deaths of medical workers.” In

  order to quell the negative impact of the new crown epidemic, the vast majority of the population needs to be vaccinated. This fact is already well understood by most people. . But many people may not know that there is a very sought-after resource-macaques in the development of the new crown vaccine.

  The macaque is an omnivorous animal, mainly vegetarian. Its brain structure, physiological functions and genes are similar to humans, and it has advanced cognitive behaviors. After long-term experimental comparisons, researchers found that rhesus monkeys and cynomolgus monkeys are the most ideal experimental animals for new drug development in the clinic. However, one of the problems facing scientists all over the world is that the breeding cycle of experimental monkeys is very long, and the years of postgraduate studies are not even enough for the generation of experimental monkeys, and related experiments cannot be carried out.


  The good news is that scientists from Shanghai have developed an efficient and stable non-human primate reproduction acceleration technology that can shorten the natural breeding time of cynomolgus monkeys from 5 years to less than 2 years.


  The good news is that scientists from Shanghai have developed an efficient and stable non-human primate reproduction acceleration technology that can shorten the natural breeding time of cynomolgus monkeys from 5 years to less than 2 years.

  On May 4, the journal National Science Review published an online research paper entitled "Accelerated Passage of Genetically Modified Monkeys Based on Exogenous Hormone-induced Precocious Puberty". The research was funded by the Chinese Academy of Sciences for Brain Science and Intelligent Technology. The team of Excellence Innovation Center (Institute of Neuroscience), Shanghai Center for Brain Science and Brain-like Research, and Key Laboratory of Primate Neurobiology of the Chinese Academy of Sciences, Sun Qiang, Xiong Zhiqi and Liu Zhen teamed up.

The king standing at the top of the chain of contempt


  In different scientific experiments, scientists will use different experimental animals, such as macaques, mice, rabbits, pigs, fruit flies, nematodes, zebrafish, etc. Because the macaque is more similar to the human brain structure and immune system, macaques play a vital role in the research of advanced brain cognition. Because rhesus monkeys are extremely similar to human DNA, they can be infected with human-specific infectious diseases, such as polio, AIDS, dysentery, tuberculosis, etc., which we often talk about. Artificial experiments can pass infectious diseases infected by rhesus monkeys. Research out related vaccines.


In different scientific experiments, scientists will use different animals.


  In addition, in pharmacology and toxicology research, reproductive physiology research, stomatology research, geriatric research, organ transplantation and ophthalmology research, endocrine disease and teratology research, oncology research, etc., macaques are inseparable Silhouette. For the research and development of new drugs related to brain diseases, only experiments on non-human primates and other large animals prove to be effective, and then human clinical trials can effectively reduce the failure rate.

  It is no exaggeration to say that rhesus monkeys have an inestimable role in helping humans study the pathogenesis of diseases, as well as drug development and vaccine evaluation. Because of this, non-human primate experimental animals represented by monkeys are the experimental subjects that many scientists engaged in life science research dream of. They are the kings at the top of the experimental contempt chain.

  Generally speaking, there are two main types of monkeys that can be used for experiments: The first type is a variety of wild monkeys that can be used for various animal behaviors and regional distribution in the wild, such as golden monkeys and white-headed monkeys. Leaf monkey, black-headed leaf monkey, etc The second category is monkeys dedicated to vaccines, drug research and development experiments, physiological experiments and other projects. Now the dedicated experimental monkeys are generally rhesus monkeys.

  Rhesus monkeys are typical animals of the Macaca genus. They have a stout body, short tail, brown head, brown-gray or brown-yellow back, orange-yellow or orange-red underside, and pale gray-yellow ventral surface. The average adult body length is about 50-60 cm. Widely distributed in the vast areas of southern China, northern India, and some Asian countries such as Afghanistan, Pakistan, Nepal, Myanmar, Vietnam, Thailand, etc., it mainly inhabits rocky cliffs, river valleys and dense forests or sparsely forested rocks on the banks of rivers. I like to live in groups, and often move together in large groups of more than ten or even hundreds.


  Among all the monkeys, because of the relatively large number of rhesus monkeys, they are highly adaptable, easy to domesticate and reproduce, and are physiologically close to humans. Therefore, they are ideal experimental animals for research in various disciplines such as biology, psychology, and medicine. . The monkeys commonly used in experiments are mainly rhesus monkeys and cynomolgus monkeys. Among them, rhesus monkeys are mainly distributed in my country and India, and cynomolgus monkeys are mainly distributed in some countries and regions in Southeast Asia such as Vietnam, Cambodia, Laos, Myanmar, Thailand, Bangladesh, Malaysia, the Philippines, and Indonesia.



The reproductive development process of primates represented by monkeys is very different from that of rodents.


  Because cynomolgus monkeys multiply faster, and their weight of 4 kg to 5 kg is smaller than the average 7 kg rhesus monkey, resulting in a correspondingly smaller amount of medicine. Therefore, since the 1970s, experimental use Monkey apps have fully turned to cynomolgus monkeys.

  The United States has been experimenting with monkeys since the last century, and is the country with the most monkeys in the world. According to statistics from the U.S. Department of Agriculture, the consumption of monkeys in the United States hit a record high in 2017, with more than 74,000 monkeys used throughout the year, including commercial dosages such as drug safety evaluation and basic experimental dosages. The United States once mainly relied on India to supply rhesus monkeys, but since 1978, due to various reasons such as religion and animal protection, India stopped exporting to the United States. The cynomolgus monkeys in Southeast Asia have become an alternative to imports from the United States. The Chinese monkey industry took advantage of the demographic dividend and the opportunity of reform and opening up at that time to quickly replace Southeast Asia to fill this market gap and become the world's largest non-human primate laboratory animal. Supply country. The experimental monkeys bred in China are mainly cynomolgus monkeys, accounting for about 80%-85% of the total industry. Since cynomolgus monkeys are not native to China, all species of monkeys need to be imported from Southeast Asia.

Magical accelerated generation technology


  The reproductive development process of primates represented by monkeys is very different from that of rodents. Mice start spermatogenesis soon after birth, and sperm can be formed 20 days after birth. Primates do not start sperm development until they enter puberty. Male cynomolgus monkeys and rhesus monkeys often do not enter puberty until they are 3 years old. The time to produce sperm for the first time is generally around 4 years old. It can be seen that the commonly used non-human primate experimental animals cynomolgus monkeys and rhesus monkeys have a very long prepubertal period.


  As a precious animal resource, experimental monkeys are not like industrial products that can be produced immediately after placing an order. The first batch of second-generation "commercial monkeys" can only be released for at least 8 years before entering a relatively stable supply cycle .


  Generally speaking, monkeys need five years from birth to sexual maturity, and about five and a half months from pregnancy to childbirth, usually one litter per litter. The baby monkey grows slowly, lying on the mother monkey like a small pendant throughout the lactation period. As a precious animal resource, experimental monkeys are not like industrial products that can be produced immediately after placing an order. The first batch of second-generation "commercial monkeys" can only be released for at least 8 years before entering a relatively stable supply cycle. .

  Past studies have shown that the hypothalamus-pituitary-gonad axis plays a key regulatory role in mammalian reproductive development. After entering puberty, the hypothalamus secretes gonadotropin-releasing hormone GnRH to the pituitary to promote the pituitary to secrete and release gonadotropin . Gonadotropins (FSH and LH) act on the testis of male individuals through endocrine, prompting the somatic cells in the testis to secrete testosterone and other gonadal hormones, and initiating the proliferation and differentiation of germline stem cells to develop into sperm.

  In response to the limitation of the long generation cycle of non-human primates, Sun Qiang’s team from the Center for Excellence in Brain Intelligence of the Chinese Academy of Sciences developed a technology for accelerating reproduction of cynomolgus monkeys based on testis xenotransplantation in 2016. Lateral testes were transplanted under the skin of castrated nude mice to obtain sperm that can produce offspring individuals, and then established an accelerated reproduction technology that can obtain cynomolgus monkeys within 30 months. However, the testis xenotransplantation technology yields a small number of sperm, and has no autonomous fertilization ability. It requires single sperm injection to complete fertilization, and the fertilization rate and embryo development rate are low. Therefore, there is an urgent need to develop a more efficient and stable inhuman spirit. Technology for accelerating reproduction of long animals.

  This time, researchers gave the juvenile cynomolgus monkeys (0.5 years old, 1 year old, 2 years old) exogenous FSH and testosterone, and found that the experimental monkeys had normal vitality after 4-11 months of treatment with exogenous FSH and testosterone. Sperm. Through this method, the minimum age for obtaining sperm cynomolgus monkeys is 15 months. The obtained sperm can be efficiently used for embryo construction, and individual offspring can be obtained (within 22 months). The birth rate of transplanted embryos is close to that of natural breeding.

  This technology not only greatly reduces the reproduction and passage time of cynomolgus monkeys, shortens the 5 years that normally takes for natural breeding to less than 2 years, but also solves the problem of low fertilization rate and embryo development rate of testis xenotransplantation acceleration technology. .

  On this basis, researchers have made persistent efforts to use this technology to accelerate the breeding of MECP2 transgenic monkeys and PRRT2 knockout monkeys, and successfully obtained the F1 and F2 generations of MECP2 transgenic monkeys and the F1 generation of PRRT2 knockout monkeys.

  This means that by acting on the hypothalamic-pituitary-gonadal axis of cynomolgus monkeys by exogenous hormones, the accelerated reproduction of cynomolgus monkeys can be achieved stably and efficiently, and wild-type, transgenic and gene-edited monkey generations can also be obtained. The brain science research, developmental biology and even drug research and development are of great significance.

How long will it last if a monkey is hard to find


  The sudden new crown pneumonia epidemic has plunged the world into a quagmire, and countries around the world have begun to invest heavily in clinical research and development of vaccine experiments. Taking the United States as an example, many pharmaceutical companies that develop vaccines such as Johnson & Johnson and Pfizer are facing the serious problem of lack of monkeys for animal experiments on vaccines. In fact, it is not only the United States that has a shortage of experiments, but also other countries, even China, a large monkey-producing country, is no exception.

  Relevant data shows that there are currently more than 240,000 of the two main experimental monkeys in the country. Except for young monkeys and breeding monkeys, the actual stock of commercial monkeys is about 100,000. If you remove the ones that have been booked or underwritten overseas, they are too young or " There are only about 30,000 "menopausal" monkeys in the country.

  At present, my country's own experimental demand for experimental monkeys in one year is close to 30,000, of which 25,000 cynomolgus monkeys are consumed every year in preclinical trials of new drugs. At the end of 2018, the state specially approved some import applications for monkey farms, but they could no longer meet the supply gap. Data shows that the annual output of China's experimental monkeys in 2019 is less than 35,000, but the total demand for export plus domestic sales is nearly 50,000, and there has been a huge gap in demand.

  It is no exaggeration to say that experimental monkeys are a more precious resource than chips. The price of the experimental monkey has soared from the previous level of 15,000 to more than 60,000 yuan, and it is still in a priceless situation. Now, Chinese scientists have developed a technology to accelerate monkey reproduction. If this technology can be applied as soon as possible, it will be able to solve the monkey shortage problem from the source.

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