91色情片

THE race to develop vaccines against covid-19 got off to a flyer, but with dangerous new virus variants, stark inequalities in access to vaccines and few vaccination options for children, the world still needs all hands on deck. Last week, a virtual meeting run by the New York Academy of Sciences called showcased the most promising new candidates.

Codagenix: Nose drop

So far, all approved covid-19 vaccines have been injectable. Another option is a nose drop, says Robert Coleman, CEO of biotech company , in Farmingdale, New York.

Codagenix鈥檚 technology uses a live, but weakened, version of the coronavirus that causes covid-19 to provoke an immune response. This approach makes the company the black sheep of the vaccine community, admits Coleman. 鈥淭hey are the most efficacious form of vaccine, they are single dose, they provide broad and robust immunity, but most people consider them to have safety risks.鈥�

The reason? Conventionally, such vaccines are produced by a trial-and-error process in which the virus is grown in animal cells until it acquires enough mutations to make it harmless to humans.

Viruses in such vaccines can occasionally revert back to the dangerous type and start circulating among people, setting off new waves of disease.

However, Codagenix synthesises its coronavirus genome from scratch, and introduces genetic changes that weaken the virus. The enfeebled virus can replicate sluggishly and stimulate the immune response, but doesn鈥檛 cause disease. The team believes that the genome is so heavily modified 鈥� it has 283 mutations compared with the original virus 鈥� that there is no risk of it reverting back to being dangerous. 鈥淲e call it death by a thousand cuts,鈥� says Coleman.

One advantage of this approach is that the immune system encounters the entire virus, so mounts a broad response, potentially allowing it to be more effective against variants, although this is yet to be tested.

The vaccine is administered in a single dose dripped into the nose. It is currently in phase I trials (see 鈥�Trial phases explained鈥�). The vaccine will also be tested on children, says Coleman.

Valneva: A whole, inactivated virus

A vaccine developed by in Saint-Herblain, France, leans on past successes by containing inactivated, whole virus, which cannot replicate but still induces an immune response.

Conventionally, such viruses are inactivated using chemicals or ultraviolet radiation. The inactivated virus is then purified, concentrated and mixed with a substance called an adjuvant, which boosts the response of the immune system. It is a and commonly used in many flu vaccines.

They are exceptionally safe, says Thomas Lingelbach, Valneva鈥檚 CEO, so the vaccine could be given to vulnerable populations such as those at risk of an allergic reaction from other types of vaccine.

The two-shot vaccine is in phase I/II trials, with plans for testing in children.

Inovio: DNA, not RNA

Two of the first crop of covid-19 vaccines 鈥� made by Pfizer/BioNTech and Moderna 鈥� use messenger RNA (mRNA), which is injected into muscle cells. The cells then translate the RNA鈥檚 genetic code and make viral proteins that stimulate an immune response.

Both vaccines provide around 95 per cent protection against severe covid-19. But the technique has downsides, not least that the mRNA has to be kept blisteringly cold during distribution and has a short shelf life once unboxed.

That is where DNA can outperform mRNA, says J. Joseph Kim, CEO at , in Plymouth Meeting, Pennsylvania.

Inovio has synthesised a DNA version of the coronavirus鈥檚 spike protein gene 鈥� which is made of RNA in the actual virus 鈥� and inserted it into circles of DNA called plasmids. These are blasted into the skin using a reusable 鈥済un鈥�. The DNA is taken up by skin cells and transcribed into mRNA, which is then translated into 鈥渕assive quantities鈥� of spike protein, says Kim, eliciting a strong immune response.

DNA vaccines don鈥檛 require frozen storage, and have a one-year shelf life at room temperature and up to five years in a refrigerator. Inovio鈥檚 vaccine only contains DNA and water, so is also less likely than some other vaccines to provoke an allergic reaction. Inovio鈥檚 two-dose vaccine is in phase II trials.

CureVac: Natural RNA

Another twist on mRNA vaccines is being developed by in T眉bingen, Germany. Both of the existing RNA vaccines for covid-19 use mRNA that has been chemically modified so that it can evade the defences of the innate immune system, which degrades foreign mRNA on the (usually correct) assumption that it is from a virus. Modification is carried out by adding synthetic nucleotides, the building blocks of RNA, that aren鈥檛 found in nature.

However, these modifications dampen innate immunity. This is the first phase of the immune response and is vital to drive adaptive immunity: antibodies that learn to recognise the virus and the white blood cells called T-cells that destroy it.

CureVac uses mRNA built from , stabilised in a different way. This induces a strong innate immune response as well as an adaptive one, says Stefan Mueller at CureVac.

The company is also developing a portable mRNA printer, in collaboration with Tesla, to rapidly manufacture mRNA. These printers could be taken to where the vaccine is needed and used to produce vaccines on demand.

CureVac鈥檚 vaccine is in . The UK says it will buy 50 million doses if it is approved.

Vaxart: A vaccine pill

The campaign to vaccinate everyone is a race against time, especially as more dangerous variants of the virus emerge. According to Sean Tucker, chief scientific officer of biotech company in San Francisco, one rate-limiting step is getting people to a vaccination centre and injecting them. His solution is to eliminate the needles.

Vaxart is at the early stages of developing a covid-19 vaccine in pill form that could be distributed by post. 鈥淭he vaccine comes to you,鈥� says Tucker.

Vaxart鈥檚 pill contains a weakened human adenovirus called Ad5 loaded with genes from the coronavirus 鈥� both the spike protein and the , which forms the virus鈥檚 shell 鈥� plus an adjuvant. The tablets are designed to break down in the small intestine, stimulating an immune response.

Results of a phase I study announced at the meeting show that the pill elicits a response from T-cells in the bloodstream and antibodies in the lining of the nose. However, it didn鈥檛 produce antibodies in the bloodstream, raising questions as to its potential efficacy. This news caused the company鈥檚 share price to crash. However, Tucker points out that the study met its stated goals and says the company will press on.

CanSino Biologics: A child-friendly jab?

Getting news out of China鈥檚 leading vaccine programmes, run by the companies Sinovac and Sinopharm, has proved difficult. But one Chinese company has revealed its hand. CanSino Biologics, in Shanghai, is developing a vaccine similar to the Oxford/AstraZeneca one.

CEO Xuefeng Yu told the conference that the vaccine is in phase III trials. The vaccine has already been administered to more than 150,000 Chinese military personnel with no reported ill effects, although there is no efficacy data because there are so few cases in China, says Yu.

As part of a phase II trial in Tiazhou, Jiangsu province, 30 children aged between 6 and 12 were given two shots. Yu says the firm is now analysing safety and immunology data.

GCVI: Vaccinating the world

As the World 91色情片 Organization warns, the pandemic won鈥檛 end until the whole world is vaccinated.

Peter Hotez at Baylor College of Medicine in Houston, Texas, and his colleagues have now set up the Global Coronavirus Vaccine Initiative (GCVI) to get covid-19 vaccines to the world鈥檚 poorest people. They have a vaccine in phase II trials in India, and it is 鈥渁bout as straightforward and simple a vaccine as you can imagine鈥�, says Hotez. It consists of a vital bit of the spike protein, grown in transgenic yeast and mixed with an adjuvant.

This type of vaccine has a great track record and is similar to a common hepatitis B vaccine. Such vaccines cost about $3 for two doses. Experience suggests that it will be suitable for children.

The GCVI will seek emergency use authorisation in India within months and is negotiating with manufacturers in Africa, Latin America and the Middle East.