HIV Vaccine Progress And Challenges

Overview of HIV and its impact on the immune system

Describe about the HIV Vaccine Progress and Challenges.

Human immunodeficiency virus is a deadly virus that has shaken the world of scientists since the time it was discovered among different citizens. This virus affects the immune system in a way that its interferes with the immune system create situations where other infections like tuberculosis, influenza and other opportunistic infections can easily invade the human being. The immunity system loses its capability to fight with the new infections due to the interruption in its activity by the already present HIV virus. Over decades, it has resulted in loss of huge number of lives and scientists have yet not been able to come out with effective vaccine against it. Various researches all over the world are still being conducted to make the world a safe place from this virus. The essay would therefore contain the various challenge and progresses in the field of the research of HIV vaccine in the present generation.

It has been noted that over the decades, different medications have been proposed which has helped in stabilisation of the symptoms of aids but has not cured or protected an individual from such viruses (Kwong & Mascola, 2012). Vaccines have therefore become necessary to protect an individual from acquiring the infection so that the concern of curing or treatment does not arise. The main challenge faced by the scientists while preparing the vaccine for HIV is that the proteins present on the viral envelope are quite different and do not match with the other viruses whose vaccine has been created. Therefore, preparations of primers that would match the antibodies occurring from  adaptive immunity have not become successful. To explain clearly, a person suffering from HIV infection would develop antibodies against it and mimicking these antibodies to create a vaccine as a protective measure for normal healthy individuals to protect them from HIV, has not been possible yet. The victims have not survived long enough after HIV infection to make this technique successful (Ensoli et al., 2014).

Another challenge often faced by the scientists is that killed HIV virus becomes unresponsive and fail to act as antigen when administerd into an animal model to produce antibodies against it. Other virus when killed but administered into a healthy being evokes response and thereby helps in collecting antibodies from this individual to produce mimicked antibodies and use it as vaccine to other individuals. This is not possible by HIV viruses. Moreover live viruses cannot also be used to produce antibodies due to ethical issues and regulations. Therefore scientists often face challenges in creating a proper vaccine (Koff, 2012).

Challenges faced by scientists in HIV vaccine research

There is another challenge faced by the scientists while preparing vaccine is the evolving nature of the HIV virus. HIV virus undergoes high rate of mutation within the body of infected individual. They are not affected the pressure imposed on them by the immune system of the body. They respond with high efficiency to the various selective pressure of the immune system and alters themselves through various mutation to remain unaffected by the both antibody mediated immunity and cellular immunity (Ensoli et al., 2014). Due to this evolving nature of the viruses, often scientists have found it difficult to cope up with the researches required to form an effective vaccine.

Another challenge that is faced by the scientists during the preparation of the vaccine is the huge amount of genetic variance and genetic divergence that reside in the various isolates of the HIV virus. The ability of the HIV virus to be integrated into the DNA of the host and the error prone nature of the HIV reverse transcriptase lead to a wide genetic diversity in the HIV virus over time (Haynes & McElrath, 2013).  HIV virus is found to possess a large number of clades as well as subtypes. Therefore, creation of an effective vaccine would require the vaccine to evoke an immune response that would cover all the subtypes and clades of HIV. This implies that a vaccine of a broad spectrum is required to prevent a huge number of subtypes to cause infection. Therefore, efficacy of the vaccines produced till date has shown little success (Esparza, 2013).

Therefore, the preparation of a vaccine depending upon the antibody response of an individual is not taken into account by the scientists. Rather, they have accepted the development of vaccine that would solely aim at the response evoked by the cytotoxic T lymphocytes.

Broadly neutralizing antibodies called the bNAbs are mainly researched which are produced when scientists focus on the envelop based vaccines. These antibodies usually act by directly binding to the envelope protein of the HIV and prevent their further activities. However, they are very difficult to produce as it requires high somatic hyper mutation which is a prolonged process that ultimately fails to stop the rapid co evolution of the virus. High degree of sequence variability in the envelope gene in the virus makes this process a lengthy one (Martin & Siliciano, 2016).

After the 2009 trial of the RV144 phase 3 trial in Thailand, two international teams had been working extensively to increase the efficacy level of 31.2% found in the trial in Thailand. In 2012, researches conducted have shown that IgG antibodies to HIV-1 Env V1-V2 have shown that it can correlate inversely with infection risk and thereby supports the fact that antibodies, which bind to the V1V2 Env region, can take active part in the prevention of the enzyme. To carry forward with the research, four more V2 monoclonal antibodies were selected from the already established RvV144 vaccine but it was found that they could not neutralized the HIV-1 CRF01_AE tier 2 viruses. However, they were easily binding with the surface of CRF01_AE tier 2 virus-infected CD4+ T cells. This proved that they were efficient enough to cause antibody dependent cellular toxicity (Kim,Excler & Michael, 2015). Just like the Anti-V1V2 BnAbs RV144 V2 mAbs, RV144 V2 mAbs were also found to bind the same V2 Env region. A point that was found in the studies with  RV144 V1 mAbs is that like Anti-V1V2 BnAbs they cannot bind glycans and also the V2 region where the mAbs can bind shows variation in their conformation. This is mainly due to the fact that Anti-V1V2 BnAbs have a beta strand but the mAbs have an alpha helix. However,  it has raised the vaccine induced immune to near about 50 % showing a progress in the field of HIV vaccine. This has raised expectations that V2-antibody-mediated ADCC of infected CD4+ T cells can thereby act as a potential mechanism of protection against HIV.

Developing vaccines that cover different HIV subtypes and clades

However, an aspect that has been found here is that in presence of the low tier anti Env IgA antibodies, the antibody-dependent cellular cytotoxicity (ADCC) shows inverse correlation with infection risk in RV144 which thereby shows that anti-Env IgA antibodies reduces the protective effects of IgG antibodies and activities of CD4+ T cell helper responses (Streeck et al., 2013). To simplify, it states that IgA antibodies in serum can inturn block the ADCC activity of IgG anti-Env antibodies. These researches are still going on and has been planned to be conducted in South Africa on non human primates with the similar principles of RV144 but with a different HIV subtype this time (Watkins, 2012).

A further progress was made when it was tested in South Africa that gave more insight into the modern attempts to develop a vaccination against HIV. Based on the RV144 vaccine model, the P5 vaccine regimen was prepared by the scientist, which used the application of the ALVAC prime as well as resulted in protein boost. This regimen was examined on the HIV Vaccine Trials Network 100 phase 1/2a study in South Africa. Depending upon the this regimen, another study was proposed to be set in the late 2016 with an aim to improve the results of RV144 vaccine (Russell & Marovich, 2016)

An important progress was also found in the preparation of mosaic vaccines against HIV. This research was conducted to handle the overcoming of HIV-1 virus diversity. The technique was mainly based on the induction criteria of the cross reactive Tcell responses to that of the HIV-1 virus. The vaccines were designed in silico and are known as the conserved and mosaic vaccines and were constructed with the aim of creating a broad coverage across both the CD4 and CD8 T cells epitopes. These were conducted on Nonhuman primates to prove the efficiency.  Phase 1clinical trials began in the year 2014 and are going on to establish a vaccine that can tackle the HIV infection (Haynes et al., 2014).

It can be concluded that even in spite of several difficulties and challenges, scientists all over the world have dedicated themselves in the creation of a vaccine that would relieve mankind from the burden of the infection. Scientists have taken out different ways to tackle the genetic divergence of the virus and create a vaccine that would be able to treat the virus and handle the genetic divergence with high efficacy. Due to the high rate of mutation that they can undergo, producing vaccines have become extremely complex (Fauci, Folkers & Marston, 2014). However, as the scientists have already reached an efficacy level of 50%, the world can hope a day when the scientists can give us a 100% efficient vaccine that would relieve humankind from this dangerous virus thereby changing the face of the world with this scientific revolution.

References:

Ensoli, B., Cafaro, A., Monini, P., Marcotullio, S., & Ensoli, F. (2014). Challenges in HIV vaccine research for treatment and prevention. Frontiers in immunology, 5, 417.

Esparza, J. (2013). A brief history of the global effort to develop a preventive HIV vaccine. Vaccine, 31(35), 3502-3518.

Fauci, A. S., Folkers, G. K., & Marston, H. D. (2014). Ending the global HIV/AIDS pandemic: the critical role of an HIV vaccine. Clinical Infectious Diseases, 59(suppl 2), S80-S84.

Haynes, B. F., & McElrath, M. J. (2013). Progress in HIV-1 vaccine development. Current opinion in HIV and AIDS, 8(4), 326.

Haynes, B. F., Moody, M. A., Alam, M., Bonsignori, M., Verkoczy, L., Ferrari, G., … & Kelsoe, G. (2014). Progress in HIV-1 vaccine development. Journal of Allergy and Clinical Immunology, 134(1), 3-10.

Kim, J. H., Excler, J. L., & Michael, N. L. (2015). Lessons from the RV144 Thai phase III HIV-1 vaccine trial and the search for correlates of protection. Annual review of medicine, 66, 423-437.

Koff, W. C. (2012). HIV vaccine development: challenges and opportunities towards solving the HIV vaccine-neutralizing antibody problem. Vaccine, 30(29), 4310-4315.

Kwong, P. D., Mascola, J. R., & Nabel, G. J. (2012). The changing face of HIV vaccine research. Journal of the International AIDS Society, 15(2).

Martin, A. R., & Siliciano, R. F. (2016). Progress toward HIV eradication: case reports, current efforts, and the challenges associated with cure. Annual review of medicine, 67, 215-228.

Russell, N. D., & Marovich, M. A. (2016). Pox-Protein Public Private Partnership program and upcoming HIV vaccine efficacy trials. Current Opinion in HIV and AIDS, 11(6), 614-619.

Streeck, H., D’Souza, M. P., Littman, D. R., & Crotty, S. (2013). Harnessing CD4+ T cell responses in HIV vaccine development. Nature medicine, 19(2), 143-149.

Watkins, D. I. (2012). Update on progress in HIV vaccine development. Top Antivir Med, 20(2), 30-1.