There is currently no vaccine available that can prevent human immunodeficiency virus (HIV) infection. Why do scientists believe that an effective and safe HIV vaccine can teach the immune system how to fight HIV? I had a closer look at their latest research of HIV vaccines.

The immune system

The immune system consists of a variety of cells that protect the body from diseases and other harmful substances caused by pathogens, such as bacteria, viruses, fungi and parasites. An immune response is divided into four steps:

1. The presence of an infection caused by a pathogen must be detected.
2. The infection must be either eliminated or controlled.
3. The immune response itself must be controlled in order to avoid causing damage to the body, e.g. by developing an autoimmune response or allergy.
4. The immunological memory must be developed to allow for an immediate and stronger response against a reoccurring infection.

There are two main departments of the immune system: innate and adaptive:

The innate immune system consists of non-specific mechanisms, including physical barriers, chemical barriers and white blood cells. It is ready to resist a pathogen at any time, but can be tricked by many pathogens. This part of the immune system depends on a group of proteins and cells that identify features of a pathogen that are different from human cells.

The adaptive immune system is activated when the innate immune response fails to eliminate the pathogen. In contrast to the innate immune system, it is not readily available and can take days to respond to a pathogen; however, it is more efficient in eliminating infections. It consists of lymphocytes that can recognise and respond to an enormous variety of different pathogens (several thousand billion) by recognising their unique antigens. This part of the immune system can develop an immunological memory. The adaptive immune system includes two types of lymphocytes: B lymphocytes (B-cells) and T lymphocytes (T cells).

• An activated B-cell produces antibodies that bind to and neutralise pathogens or prepare them for destruction by other immune cells.
• An activated T-cell can develop into cytotoxic T-cells, helper T-cells, or suppressor T-cells.

Some of the B-cells and T-cells can develop into memory cells, which can result in life-long immunity against a pathogen.

Vaccines strengthen the immune system

Vaccines teach the immune system how to recognise and defend against certain pathogens by presenting antigens that are unique for each pathogen. Vaccine antigens can include:

• Live pathogens that are either weakened or inactive
• Individual components of the pathogen, such as proteins
• Genetic material of the pathogen, e.g. DNA or RNA

Most available vaccines are preventive vaccines (also called prophylactic vaccine). They are given to healthy people who do not have the disease. This type of vaccine allows the immune system to create antibodies and train immune cells to prevent the development of many diseases, such as polio, chicken pox, mumps, measles and influenza.

In contrast, therapeutic vaccines are given to people who already have a disease. These vaccines are designed to strengthen the immune system’s response to a disease.

The ups and downs of HIV vaccine development

Existing antiretroviral therapies can dramatically prolong the lives of patients with HIV. However, these therapies are unable to eliminate HIV infection due to the persistence of the latent HIV reservoir. Thus, patients with HIV infection are required to take antiretroviral therapies every day until the end of their lives.

In contrast, HIV vaccines have the potential to either provide long-term control of HIV or eliminate HIV completely. However, there are many challenges for scientists who want to develop effective HIV vaccines:

• HIV is extremely diverse, and different types of HIV can differ up to 35% in their envelope proteins.
• HIV mutate rapidly.
• The development of vaccines is very cost-intensive. Studies which evaluate the risk of HIV infection are called HIV vaccine efficacy studies. These studies can only be performed in a large population with high HIV incidence. Low HIV incidence rates would require an extremely large population and huge costs to get results.

Scientists are currently following two main approaches for vaccine development:

1. Developing antigens that cause the immune system to produce broadly neutralising antibodies.
2. Inducing the production of functional (non-neutralising) antibodies with other potential anti-viral functions.

Scientists have already developed several different vaccines that have resulted in a mixed level of HIV protection. A list of selected vaccines can be found below.

• Early HIV vaccines, such as VAX003 and VAX004, focused on developing antigens based on HIV envelope proteins. Scientists hoped to stimulate the production of neutralising antibodies, which block HIV. These types of vaccines did not show a protection against HIV.
• Therefore, scientists focused on vaccines that induced T-cell responses against HIV, such as STEP and Phambili. These vaccines did not prevent HIV infection and had no effect on the amount of HIV in the body. STEP was even associated with an increased risk of HIV infection in a subgroup of study participants, although this faded over time.
• In addition, a study to assess the DNA vaccine HVTN505 was stopped early due to lack of vaccine efficacy.
• The RV144 vaccine proved for the first time that a vaccine can reduce the risk of HIV infection by 60% at 12 months and by 31% at 3.5 years. This vaccine consists of two different types of vaccines (ALVAC-HIV [the prime] and AIDSVAX [the boost]), which produces only very weak neutralising antibodies.
• Many scientists are trying to improve the RV144 vaccine’s HIV protection with advanced vaccines such as HVTN097 and They do this by tweaking the protocol and by testing vaccines in different populations.
• In addition, mosaic vaccines such as HIV-V-A002 are currently being tested. These aim to generate immune responses that can detect many different parts of HIV.
• Another approach scientists use is passive immunisation, which is an administration of antibodies such as VRC01 to prevent infection. The immune system does not generate these antibodies itself.
• The Tat vaccine uses the Tat protein as an antigen, which plays a crucial role in HIV gene expression and disease progression. This type of vaccine has the potential to interrupt HIV development at a very early stage. Following promising results from Phase 1 and 2 studies, Phase 3 studies are being developed.

Scientists are fighting against HIV by using their knowledge and investing a lot of their time to develop vaccines that could control or prevent HIV infections. Today is vaccine awareness day, which provides us with a great opportunity to thank not only those amazing scientists, but also the many volunteers and healthcare professionals who are involved in vaccine studies. They are working to find a successful HIV vaccine that could control or even eliminate HIV.

Susanne Ulm is a Medical Writer part of our Prime team at Prime Global and has been with the company since November 2014. Susanne has broad experience in different therapeutic areas, and has a passion for communicating science to different types of audiences.