Understand how experimental HIV vaccines based on viral vectors are made

Many of the HIV vaccine candidates being tested in clinical trials use viral vectors to transport fragments of the human immunodeficiency virus into the body so that they can generate an immune response. Some of the experimental vaccines based on viral vectors are being tested in boost-boost regimens with alternative approaches. Several different viruses have been used in the development of vectors for anti-HIV vaccines, such as adenoviruses (responsible for the common cold), viruses of the smallpox family, such as the so-called Modified Vaccinia of Ankara (MVA) or canarypox, among others.

Viruses used as viral vectors are attenuated so that they cannot cause disease and are also modified so that – in addition to their own genetic code – they can carry HIV genes (called antigens), but cannot cause HIV infection.

HIV genes that are introduced into the viral vector are known as ‘vaccine insert’. Once the candidate is injected into the body, the genetic material of the virus penetrates the cells and is able to generate proteins that, ideally, will activate the immune system to respond to HIV. This may seem simple enough, but experimental vaccines based on viral vectors present special design and manufacturing challenges. Because the manufacturing process is so complicated, more effort is needed to avoid delays in clinical testing of these viral vector-based vaccine candidates.

Lack of harmony

To develop experimental vaccines based on viral vectors, it is first necessary to design and generate the vector with the HIV insert in cells that allow the virus to grow. The viral vector is amplified several times to produce hundreds of viral particles that carry the HIV genes, which are then subjected to extensive testing.

One of the main challenges in carrying out experimental vaccines based on viral vectors has to do with chemistry, or rather, with the absence of chemistry between the vector and the insert. Sometimes they are simply incompatible. For example, if the length of the insert is too long or its configuration is not suitable for the viral vector, it may be rejected by the viral vector. In other cases, the vector virus can introduce mutations in HIV genes that may prevent the complete protein from being made once inside the body. Ultimately, these changes can affect the generation of a good immune response after vaccination. Sometimes the vector can even cut the insert, rendering it totally useless.

In some cases, the vector can tolerate insertion for a time, while in others, it will reject it outright. In any case, it represents a setback for the production of the vaccine candidate. Therefore, it is important to analyze the stability of these vectors during the early stages of vaccine development. This is achieved by subjecting these vectors to a series of stress tests to assess whether they are stable enough to be tested in a clinical trial. These tests examine the ability of these vectors to express HIV proteins in cells and small animals. Even after completing this process, it is possible that the vector can reject the insertions, so it is not uncommon for this cycle to be repeated several times before obtaining a stable vector that expresses HIV proteins and can be brought into trials. 

It seems that it still takes some time for us to wait for a vaccine that can actually be applied en masse.