Article on vaccinating monkeys against yellow fever published in Vaccine

A group of Bio-Manguinhos/Fiocruz collaborators carried out a study on golden-headed lion tamarins at the Primatology Center in the state of Rio de Janeiro to check the safety and immunogenicity of different yellow fever vaccines. Neotropical monkeys are severely affected by yellow fever and the disease could have a devastating impact for the endangered golden lion tamarins (Leontopithecus chrysomelas) of the same genus as the animals studied in this article.

It was after the outbreak of the disease in 2017/2018 that the senior scientific advisor at Bio-Manguinhos/Fiocruz, Marcos Freire, began this work, culminating in a scientific article that was published in the journal Vaccine (Issue 48/2025), entitled "Safety and immunogenicity of different 17DD yellow fever vaccines in golden-headed tamarins (Leontopithecus chrysomelas): Inhibition of viremia and RNAemia after homologous live-attenuated vaccination".

Marcos Freire talks about the epizootics that were occurring with the golden lion tamarins. "Between Casimiro de Abreu and Silva Jardim, there is the Poço das Antas reserve, which has a project to reintroduce the golden lion tamarin, an endangered species that was recovering during this period. What we found, after a study that took an old census and the new census after the outbreak, was a loss of 32% of the golden lion tamarin population in the region. That was a blow, as it really is a significant loss in a population that was already not so large. We decided to vaccinate them and many questions arose. How resistant would these animals be to the vaccine virus? What would be the ideal dose? So this work focused on finding out what would be the best vaccine and what would be the best dose."

Then, contact was made with the Primatology Center of Rio de Janeiro and the State Environmental Institute - Inea/RJ to see if it was possible to use animals of the leontopithecus genus that were in captivity to conduct this experiment. "We decided to carry out a study to assess the ideal dose of an attenuated vaccine, an inactivated vaccine and another subunit vaccine. We assessed the attenuated vaccine in three different doses – low, intermediate and high, more or less close to the minimum human dose," he said.

For the veterinarian, the most interesting thing was that the group managed to keep these animals for a year after immunization. The aim was to observe not only the effectiveness and safety, but also the durability of this protection. "We sought to know if this protection was still able to block this viremia and RNAemia, as well as quantify the neutralizing antibodies against yellow fever. The results can also be considered as a pre-clinical study for using these vaccines in human immunization, i.e. this work will serve for future clinical studies with these approaches in humans," he explained.

In summary, the expert pointed out that the attenuated vaccine led to 100% protection a year later. In the case of the inactivated vaccine with adjuvant, with three doses, it reached over 83% protection. With the subunit vaccines, two doses were administered with adjuvants and, after a year, protection was achieved in 50% of the animals. "We are immunizing these free-living

animals (golden lion tamarins) using the parameters defined in this work. We capture the animals, apply a dose of attenuated vaccine, identify the animals, collect them pre-vaccination and, after 30 to 40 days, these animals are captured and a sample is taken. We are observing the seroconversion of these animals and the results are encouraging, with a seroconversion greater than 90%. The latest census raised expectations because we cannot say whether this was due to the vaccination of the animals. But the population rose again. It has now reached more than 4,000 individuals in the Poço das Antas region. So, in principle, there may be a relationship between the increase in this population, their re-establishment, and an immunization process that is underway," he stated.

On the subject of testing the yellow fever vaccine on other species of non-human primates, Marcos said that studies were carried out in parallel, which were then extended to other regions of Brazil, with howler monkeys, for example. "We have published another article, in this case on larger non-human primates, an animal that weighs a few kilos. We also defined the ideal dose. We gave the vaccine with the attenuated virus, the human vaccine, to these animals. We saw that 1/5 of the dose, a fractionated dose, similar to the one we use in human fractionation, was enough to immunize these animals. These results can be seen as pre-clinical studies for future use in humans. But what was interesting was to see that the attenuated vaccine is safe and effective. And we really managed to protect the animals, to produce a reasonable amount of neutralizing antibodies, and to also block viremia and RNAemia in species like the howler monkey."

The results of the study "Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.)" were published in PubMed in February 2021.