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In the midst of the world race to get a vaccine as soon as possible, in which national interests are taking precedence over global interests, and bilateral negotiations to secure millions of doses without a multinational strategy that is looming short-sighted by a virus without borders. , continue to emerge test results with the most advanced vaccines . Of the 150 investigated, about twenty have already begun human trials.

Nature publishes in its latest issue the results of rhesus macaque trials of the Ad26.COV2.S vaccines, from the Janssen company (Johnson & Johnson), and ChAdOx1 nCoV-19, from the University of Oxford and AstraZeneca.

With the first, a single dose has protected macaques against SARS-CoV-2 . It is based on adenoviral vectors that express fragments of the pathogen to stimulate an immune response. As is known, adenoviruses, linked to diseases such as the mild cold, are very effective in invading human cells. And specifically, adenovirus serotype 26 (Ad26) induces immune responses to various pathogens, both in primates and in humans.

Dan Barouch and his team from the Beth Israel Deaconess Medical Center and Harvard University in Boston, together with the experts from Janssen, have developed a series of Ad26 vectors that encode different variants of the SARS-CoV-2 spike protein and they have been tested on 52 adult rhesus macaques. They used seven potential vaccines in 32 animals and compared the results with 20 control animals that received placebo injections. Six weeks later, all animals were exposed to the SARS-CoV-2 virus. The 20 animals that received the placebo developed high levels of the virus in their lungs and nasal swabs. The best performing vaccine, Ad26-S.PP , has now entered clinical trials. The assay shows the immune response generated and the partial or total protection against SARS-CoV-2 infection in the respiratory tract.

The authors note that robust responses were achieved after a single dose, although they are confident that a two-dose regimen will produce a stronger immune response. Janssen has reported that human safety trials have already begun in the United States and Belgium. The intention is to vaccinate more than 1,000 healthy adults ages 18 to 55, and then people 65 and older.

Less viral load

In the second Nature study , Vincent Munster's team, from the Institute of Allergy and Infectious Diseases in the USA, also confirmed that the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2, which is currently in clinical trials in humans in the UK and which has been developed by the University of Oxford and AstraZeneca, it elicits an immune response and reduces the viral load in macaques exposed to the coronavirus. Those preliminary results were used to facilitate the initiation of human clinical trials of the vaccine.

ChAdOx1 nCoV-19 is designed from a weakened chimpanzee adenovirus that also expresses the spike entry protein of SARS-CoV-2. A single dose of ChAdOx1 nCoV-19, administered to six macaques 28 days before exposure to SARS-CoV-2, has been shown to be effective in preventing damage to the lungs and dramatically reducing viral load (compared to six animals). of control). Six other macaques were given a booster dose of two doses of the vaccine, 56 and 28 days before virus inoculation, which increased the immune response.

Instead, the vaccinated animals did not show an immune improvement of the inflammatory disease, something that has been observed in some preclinical studies of other vaccines against SARS-CoV. The authors indicate that there was no difference in viral clearance from the nose between vaccinated and control animals, suggesting that ChAdOx1 nCoV-19 may not prevent infection or transmission , although it does reduce disease. The Oxford vaccine has been in human clinical trials in more than 8,000 volunteers since early July.

Anyway, 10 days ago The Lancet published results of the phase I / II trial that was carried out with 1,077 healthy adults with the Oxford vaccine and that revealed that it induced strong immune responses, both cellular and humoral. Immune responses were maintained until day 56 of the ongoing trial. The researchers do not rule out that these responses are even greater after a second dose, as suggested by a subgroup of 10 individuals who received it in the study. In The Lancet results are also presented in 508 people with Chinese vaccine Cansino Biologics. 95% of participants in the high-dose group and 91% in the low-dose group showed immune responses of T-cells or antibodies on day 28 after vaccination.

Neutralization

For its part, The New England Journal of Medicine also publishes results this week on primates with the mRNA-1273 vaccine, from the company Moderna . Also carried out by members of the United States Institute of Infectious Diseases in 24 macaques, it has induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathological changes in the lung.

The primates received 10 or 100 g of mRNA-1273, which also encodes the SARS-CoV-2 prefusion stabilized spike protein , or no vaccine. Antibody and T cell responses were assessed prior to exposure to the upper and lower airways with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar lavage and nasal swab samples were evaluated by polymerase chain reaction, and histopathological analyzes and viral quantification were performed on lung tissue samples.

The 1273 mRNA vaccine induced antibody levels higher than convalescent plasma, with reciprocal titers of 50% reciprocal inhibitory dilution of live virus (ID50) of 501 in the 10-g dose group and 3,481 in the 100-dose dose. g. It also elicited the response of CD4 type 1 T (Th1) cells and low or undetectable T2 or CD8 T cells . No viral replication was recorded in bronchoalveolar fluid on day 2 after virus inoculation in seven of eight vaccinated animals. Nor did viral replication in the nose of any of the eight animals in the 100 g dose group on day 2 of infection. Limited inflammation or genome or viral antigen was observed in the lungs of vaccinated animals.

Moderna's vaccine has started phase III of clinical trials this week. Other promising ones, such as Pfizer-BioNTech and Sanofi-GSK , are not as advanced as the previous ones, which does not prevent some countries from having signed agreements for the supply of millions of doses with which to immunize their populations. .

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