HIV vaccine

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HIV vaccine candidates

The HIV vaccine is a hypothetical vaccine against the human immunodeficiency virus (HIV), which causes the immunodeficiency disease AIDS . There is currently no reliable, practical cure for HIV infection , and the development of an effective vaccine is part of many attempts to contain the spread of the virus . There are now therapies such as highly active antiretroviral therapy (HAART), but these can only reduce the viral load and thus extend the patient's life, but they do not remove the virus from the body.

An HIV vaccine is therefore believed to be probably the most effective means of preventing the spread of HIV. Research is currently being carried out on around 30 HIV vaccines worldwide.

history

The search for an HIV vaccine began shortly after HIV was discovered in 1981.

Initially, the goal of vaccine development was to develop sterilizing immunity , i.e. a vaccination that completely prevents infection. This goal is now considered unattainable. A more realistic goal is now seen to be the development of a vaccine that keeps the viral load at such a low level (height) that the onset of the disease is greatly delayed or completely prevented and makes it very unlikely that other people will be infected. However, despite great global research efforts, little success has been recorded on the way to an effective HIV vaccine: All previous HIV-1 vaccine prototypes that had the goal of achieving humoral or cellular immune responses have so far failed in clinical studies because they were unable to protect against HIV infection or to lower the viral load after infection. The reason for this is to be found in the very complex and tricky biology of the virus. HIV thus has many properties that make vaccine development difficult.

Challenges and difficulties

There are unprecedented challenges in developing a prophylactic HIV vaccine. To be mentioned here are among others:

  • the extreme genetic diversity of the viral sequences or virus strains
  • the evasion of the virus from the (also vaccine-induced) specific humoral and cellular immune reaction ( immune evasion )
  • early formation (establishment) of latent viral reservoirs
  • Antibody responses are typically virus type specific
  • there is no method for generating neutralizing antibodies with a broad spectrum of activity
  • attenuated viruses are not safe for use in humans

The high error rate of reverse transcriptase is the basis for the two greatest challenges in HIV vaccine development. On the one hand, it is the driving force behind the enormous global genetic diversity of HIV-1 - probably the greatest obstacle on the way to an effective vaccine. On the other hand, the high mutation rate offers the virus the possibility of immune evasion, i. H. an escape from the vaccine-induced immune response.

Current state of research

A vaccine that 100% protects against infection with HIV is still not available. In the course of the last 30 years, promising research approaches have repeatedly emerged, but only fewer than five of them have sufficient success potential to make it at least to phase 3 of clinical testing - i.e. to be tested on a larger group of people become. In the end, none of the agents offered demonstrable vaccination protection against infection with HIV.

The only significant exception to this is a vaccine that was researched in the RV 144 clinical study : This study, which was carried out in Thailand between October 2003 and July 2009 , involved 16,402 Thai people between the ages of 18 and 30 years. The active ingredient is manufactured by Sanofi-Pasteur . The study was funded by the US Army and carried out by the Thai Ministry of Health. The subjects were randomly distributed and blinded with the vaccine or placebo . All subjects were specifically informed how they can protect themselves against HIV infection - for example through safer sex  - and then it was left to chance who will become infected in the following years. The study participants were then given regular HIV tests for three years. The result of this study is that in the group vaccinated with the active ingredient, the infection rate with HIV was 31.2% lower than in the control group vaccinated with a placebo . In absolute numbers, this corresponds to 74 HIV-infected people in the placebo group and 51 in the vaccination group.

When interpreting this number, however, caution is advised against excessive expectations. Because of the high risk that HIV poses for the test persons, it was not ethically justifiable to specifically infect the test persons with HIV after the vaccination just to research the possible effectiveness of the vaccine.

The fact that these numbers are very small compared to the total of 16,402 participants in both groups and that the said random element related to the infection with HIV was present, prevents the resulting percentage of 31.2% from being meaningful . Nevertheless, a statistical significance of the effect can be determined using statistical methods . In other words, as a result of the study, the following statement can be affirmed: "The infection rate in the group of vaccinated persons was lower than in the control group, and this was very likely not due to statistical coincidence." In the hope of greater efficacy, new clinical trials with a modified formulation of the same vaccine will be conducted in South Africa in 2016 and run until 2020.

Current vaccine trials

The testing of an HIV vaccine is complicated and lengthy, because in a population with a high number of expected new infections, one group receives an HIV vaccine, whereas the other group is vaccinated with a placebo. In the case of the RV144 vaccine, a total of 16,402 people were included in the study. An HIV vaccine trial is currently underway after the HVTN 702 vaccine trial (Uhambo study) - a further development of the RV 144 vaccine - was discontinued after four years in southern Africa due to lack of effectiveness:

  • The randomized, double-blind Imbokodo study (HPX2008) is a mosaic vaccine developed by Janssen Vaccines that is currently being carried out on 2,600 participants in southern Africa. The vaccine consists of the following components: Ad26.Mos4.HIV particles and Clade C gp140 (250 μg) with the adjuvant aluminum phosphate .

literature

  • Andrew J. McMichael, Thomas Hanke: HIV vaccines 1983-2003. In: Nature medicine (Nat Med.) July 2003, Vol. 9, No. 7, pp. 874-80, PMID 12835708 .

Web links

Individual evidence

  1. ↑ Mariana Santos: Brazil is researching a vaccine against AIDS. Deutsche Welle , February 23, 2014, accessed March 3, 2014 .
  2. ↑ a b c D. H. Barouch: Challenges in the development of an HIV-1 vaccine . In: Nature . Vol. 455, No. 7213, 2008, pp. 613-619. PMID 18833271 .
  3. ↑ GB Karlsson Hedestam: The challenges of eliciting neutralizing antibodies to HIV-1 and to influenza virus . In: Nature reviews. Microbiology . Vol. 6, No. 2, 2008, pp. 143-155. PMID 18197170 .
  4. ↑ B. Gaschen et al .: Diversity considerations in HIV-1 vaccine selection . In: Science . Vol. 296, No. 5577, 2002, pp. 2354-2360. PMID 12089434 .
  5. ↑ S. Rerks-Ngarm, P. Pitisuttithum, S. Nitayaphan et al .: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand . In: The New England journal of medicine . Vol. 361, No. 23, December 2009, pp. 2209-20. doi : 10.1056 / NEJMoa0908492 . PMID 19843557 .
  6. ↑ a b RV144 Trial ( Memento from August 5, 2010 in the Internet Archive ). US Military HIV Research Program.
  7. ↑ World AIDS Day: Vaccination study started in South Africa. In: Pharmaceutical newspaper online. December 1, 2016, accessed December 2, 2016 .
  8. ↑ Study with potential HIV vaccine canceled. Doctors newspaper , February 3, 2020, accessed on February 4, 2020 .
  9. ↑ HPX2008 / HVTN 705: The Imbokodo Study. January 19, 2017, accessed February 4, 2020 .
  10. ↑ A Study to Assess the Efficacy of a Heterologous Prime / Boost Vaccine Regimen of Ad26.Mos4.HIV and Aluminum Phosphate-Adjuvanted Clade C gp140 in Preventing Human Immunodeficiency Virus (HIV) -1 Infection in Women in Sub-Saharan Africa - Full Text View - ClinicalTrials.gov. Retrieved February 4, 2020 .