Worldwide, vaccine candidate tests against Covid-19 are in full swing. The first promising results for two of these test vaccines are now available. Both are based on modified adenoviruses that carry parts of the Sars-CoV-2 spike protein. Both vaccine variants have now been tested in phase 2 studies in China and Great Britain. In both cases, around 90 percent of the study participants developed both antibodies against the coronavirus and immune cells. With the vaccine tested in China, however, the immune response was weaker in older participants. The phase 3 studies now underway must show whether the two vaccines can also protect against Covid-19.
Around 250 different vaccine candidates against the Sars-CoV-2 coronavirus are currently under development worldwide. Among them are almost all conceivable vaccination strategies, from classic dead vaccines that contain the killed virus, vaccines with carrier viruses to novel genetic engineering vaccines that are supposed to introduce the building instructions for parts of viral proteins into the cells. The German-based companies CureVac and Biontech and Moderna in the USA rely on these so-called mRNA vaccines. 17 vaccine candidates are currently in clinical trials with human subjects. So far, these phase 1 and phase 2 studies have initially focused on checking the tolerability of the substances and testing whether they trigger the desired immune response in the recipient. It is crucial for the effectiveness of a vaccine that the immune system produces enough neutralizing antibodies in response to the vaccine, because only these antibodies can prevent the virus from entering the cell and from multiplying. In addition, the cellular immune response, for example in the form of T cells, must also be activated.
Ad5: Cold virus infiltrates spike building instructions
Two research teams have now published initial results on two vaccine candidates, each of which was tested in phase 2 studies. The team led by Feng Cai Zhu from the Jiangsu Provincial Center for Disease Control and Prevention in Nanjing used an adenovirus for their vaccine, which causes harmless colds in humans. They genetically modified this virus in such a way that it carries the building instructions for the spike protein of Sars-CoV-2 – the crown-like outstanding surface protein with which the corona virus binds to human cells. In the body, the carrier viruses infiltrate the building instructions into the cells, which then produce the viral proteins, which then trigger an immune response. The researchers administered this vector vaccine, called Ad5, to 508 subjects of various ages. 253 participants received a high dose of around 100 billion vaccine viruses per milliliter of vaccine, 129 received a lower dose of 50 billion vaccine viruses and the rest received a placebo.
Zhu and his team used blood samples taken 14 and 28 days after vaccination to determine how strong the immune response was. Accordingly, 88 and 90 percent of the participants had developed T cells against Sars-Cov-2 on the 28th day, depending on the dose. More than 96 percent had antibodies against the virus in the blood. As side effects, the test subjects developed mainly redness and swelling at the vaccination site, but also fever, headache and exhaustion. According to the scientists, the Ad5 vaccine is therefore immunologically effective and well tolerated. However, the immune response was much weaker, especially among the older participants. As the researchers explain, this is because these people have had contact with the adenovirus in the course of their life and therefore their immune system already knows this carrier virus. This apparently also inhibits the effects of the modified Ad5 virus. “Because older people in particular are at high risk of severe course and death with Covid-19, they are an important target population for vaccination,” admits co-author Wei Chen from the Beijing Institute of Biotechnology. He and his team now want to test whether a second dose of vaccine can increase the immune response of older people to the vaccine.
ChAdOx1: chimpanzee virus as carrier
The second team of researchers may have avoided this problem by choosing a carrier virus that does not occur in humans. “The new vaccine uses a cold virus that affects chimpanzees. This has been weakened so that it cannot cause disease in humans, and then genetically modified so that it carries the code of the spike protein, ”says study leader Andrew Pollard from the University of Oxford. This modified carrier virus – christened ChAdOx1 – was administered by the researchers to 543 healthy volunteers between the ages of 18 and 55. 534 other participants received a meningococcal vaccine as a control. Blood tests showed that this vaccine also stimulated the production of antibodies and T cells against Sars-CoV-2. 28 days after the vaccination, 91 percent of the test subjects had formed neutralizing antibodies, and the T cells peaked just 14 days after the vaccination, as the scientists report. However, since the participants lacked the age group of over 55-year-olds, it is not yet possible to say whether and how well this vaccine candidate works in older people.
Nevertheless, the researchers see an important first success in these results. “There is still some work to be done before we can confirm that our vaccine will help contain the Covid 19 pandemic,” said co-author Sarah Gilbert of the University of Oxford. “But these first results are promising.” Since the results now published only cover the first 56 days of the study, it is still unclear how long the induced immune response will last. The Chinese team also has no long-term data. In view of the positive first results, phase 3 studies are already in preparation for both vaccine candidates.
Scientists who are not involved in these two studies also see them as a first important success. “The results of both studies bode well for the following phase 3 tests,” write Naor Bar-Zeev and William Moss from the International Vaccine Access Center in Baltimore in an accompanying comment. “Vaccines with adenoviruses as vectors have a lot of potential, even if these carriers were first approved by the European Commission for an Ebola vaccination on July 1, 2020.” Still, some things remain unknown with these and other vaccine forms, including the longevity of the immune response and the immune effect especially in older adults.
Source: The Lancet, doi: 10.1016 / S0140-6736 (20) 31605-6; doi: 10.1016 / S0140-6736 (20) 31604-4