Table of Contents
Introduction
A vaccine is the inoculum, or sample of microorganisms, used in active immunization (Bauman, 2014, G-19). Scientists are constantly striving to develop vaccines of maximal efficacy and safety (Bauman, 2014, pp. 496). In each vaccine, a pathogen is altered or inactivated so that it is less likely to cause illness (Bauman, 2014, pp. 496). The CDC and medical associations publish and recommend immunization schedules for children, adults, as well as specialized populations such as healthcare workers and HIV-positive individuals (Bauman, 2014, pp. 499). Recently, researchers believe that a vaccine which can target both types of the immune system responses which is cell-mediated and antibody-based is the ideal approach to prevent and eradicate HIV virus (WHO, n.d.). However, not all types of vaccines are equally safe or effective (Bauman, 2014, pp. 496).
HIV Mode of Infection
U.S. Department of Health and Human Services reports that there are seven stages to the HIV life cycle. Binding is the first step, where the virus binds to receptors on the surface of a CD4 cell (U.S. Department of Health and Human Services, 2019). The HIV envelope and the CD4 membrane then fuse and allow the virus to enter the cell (U.S. Department of Health and Human Services, 2019).
Reverse transcription then begins (U.S. Department of Health and Human Services, 2019). Once inside the cell, HIV releases the enzyme reverse transcriptase and uses it to convert HIV RNA to HIV DNA, which then enters the nucleus of the cell (U.S. Department of Health and Human Services, 2019). Upon entering the nucleus, another HIV enzyme, integrase, will then help integrate the new HIV DNA to the DNA of the cell (U.S. Department of Health and Human Services, 2019). Once HIV is integrated into the host cell DNA, it will use its systems to reproduce the necessary proteins (U.S. Department of Health and Human Services, 2019).
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New HIV proteins and HIV RNA are now able to assemble into a small vesicle on the surface of the cell into a non-mature, non-infectious virus (U.S. Department of Health and Human Services, 2019). Budding then occurs as the final step, meaning the virus releases protease to help separate the new virus from the cell membrane (U.S. Department of Health and Human Services, 2019). Once separated the HIV virus will finish assembly and become mature and infectious (U.S. Department of Health and Human Services, 2019). The process then begins again when the T-Helper cells releases HIV particles into the bloodstream giving it the ability to attack other cells (Avert, 2018).
HIV Vaccines
A therapeutic vaccine is administered to a person afflicted with a chronic viral infection, against which naturally produced antibodies are ineffective (Fondation québecoise du Sida, 2013). In other words, therapeutic vaccines aim to increase the activity of the body’s natural defences. One example of a therapeutic vaccine is PENNVAX®-GP (Fondation québecoise du Sida, 2013). In phase 1 of the HVTN 098 clinical trial, DNA vaccines were delivered through either the patients’ skin or muscle with an electroporation device (HVTN, 2019).
This device makes cell membranes more permeable to DNA using a pulse of electricity. The electroporation device was used to encourage cells to accept PENNVAX®-GP. The vaccine was delivered along with IL-12 (interleukin 12), which can stimulate the function of T-cells, which is a key component of the immune response. This particular vaccine remains on clinical trial, but the study objective was to show that PENNVAX®-GP can help the immune system reduce the amount of HIV in the viral reservoirs by generating high levels of activated and antigen-specific killer T cells in antiretroviral therapy-treated individuals (National Institutes of Health, 2018).
A preventative vaccine is administered to a person who is free of the targeted infection. By introducing a part of the virus or an inactive virus into the body, the immune system reacts by producing antibodies. If years later, the virus enters the organism, these antibodies will recognize and destroy it (Fondation québecoise du Sida, 2013). One example of a preventive vaccine is RV144. An HIV vaccine trial carried out in Thailand, Also known as the “Thai trial,” gave promising results as a way forward in HIV vaccine research with the preventive vaccine, RV144 (Safrit et al., 2016). The RV144 vaccine was utilized in the trial of over 16 000 adults ((Rerks-Ngarm et al., 2009). RV144 has two components: ALVAC-HIV, and AIDSVAX gp120 (Kirby, 2017).
The ALVAC-HIV vaccine is recombinant, using a canarypox virus, with inserted genes that code for antigenic proteins from HIV. This vaccine was used to prime the immune system and was intended to stimulate cell-mediated immunity or “T-cell responses” (The College of Physicians of Philadelphia, p.1). The T-Cells are either ‘Helper T Cells,’ (CD4 T Cells) or Cytotoxic Cells (CD8 T Cells). In antibody-mediated responses, the B Cells secrete antibodies, whereas, in cell-mediated immunity, the CD8 T Cells attack invading antigens (Bauman, 2014).
The AIDSVAX gp120 vaccine boosts immunity using an envelope protein segment from HIV subtypes B and E (Kirby, 2017). The vaccine is composed of a genetically engineered antigenic surface protein from HIV and was intended to stimulate antibody production –that is, a B cell response (The College of Physicians of Philadelphia, p.1). AIDSVAX was designed to induce the production of antibodies, causing gp120 to be stripped off of the HIV particles, effectively disabling the virus so it cannot bind or invade susceptible cells (Rerks-Ngarm et al., 2009).
The vaccines were administered at 0 weeks, 4 weeks, 12 weeks and 24 weeks (Rerks-Ngarm et al., 2009). The ALVAC-HIV vaccine was administered at each session while AIDSVAX was only administered at weeks 12 and 24 (Rerks-Ngarm et al., 2009).
The results of the trial initially revealed a 60% reduction in infection at the 6-month mark, however, at the end of the trial, the result revealed that it reduced risk of infection by 31.2% (Safrit et al., 2016). Although the results of the RV111 vaccine were promising, the two components used together they were only deemed as somewhat modest in the prevention of HIV (Rerks-Ngarm et al., 2009). The mechanisms that lead to this protection remain poorly understood, therefore RV111 was not granted use outside of the trial setting, as it didn’t meet the standards for the vaccine to be administered to the public (Fourati, Slim, et al., 2019).
Conclusion
Currently, there are no preventive or therapeutic vaccines approved by the Food and Drug Administration (U.S. Department of Health and Human Services, 2019). One of the main factors contributing to the difficulties related to treating HIV is the constant mutation of the virus. During the multiplication of the HIV cells, many of the mutate, and then multiply within the body (Bauman, 2014). When variations of the virus are created while a person is currently on HIV medicines, it ultimately causes drug-resistance. Drug resistance causes the HIV medicines being used to no longer be effective towards treating the patient’s HIV, and eventually, the treatment fails (Bauman, 2014). Knowing how HIV replicates has helped scientist research and develop ways of interrupting this process, with the hope someday of finding either a cure or a vaccine to prevent new cases of infection.
