Factors Challenging the Development of an Effective Vaccine for HIV

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Factors Challenging the Development of an Effective Vaccine for HIV

Many individuals worldwide suffer from the incurable human immunodeficiency virus (HIV) since the vaccine to prevent and control the spread and negative impacts of the contagious virus remain futile. Developing this vaccine is one of the greatest challenges that medical practitioners and organizations worldwide have encountered for the longest time since the first case was reported (Nguni et al., 2020). Life quality has been weakened significantly due to contracting the virus and the inability to control the immune systems susceptibility to various life-threatening diseases (Nguni et al., 2020). The lack of a vaccine to reduce the prevalence of HIV-1 has negatively impacted human health and wellbeing. The main research question is, What are the current barriers to developing an effective vaccine for HIV? The paper strives to highlight some of the major challenges experienced by the scientists and medical researchers that have contributed to the difficulty in developing the HIV-1 vaccine.

HIV Characteristics

During the last several decades, medical practitioners have not been able to get the HIV vaccine successfully. The only good news is that most pharmaceutical institutions have only been able to develop medicines that can be used to prolong the life of an individual who has contracted the virus (Nguni et al., 2020). HIV is one of the infections with the most unusual characteristics, making it more difficult for researchers to develop a more effective vaccine. Some of the unusual characteristics of HIV include faster replication and enraged mutations, which leads to typical vaccine approach failures (Nguni et al., 2020). HIV significantly differs from other viruses, such as polio and influenza, whose vaccines have been easier to establish.

When an individual gets infected by any form of virus, the human immune system reacts by identifying the viruses as foreign intruders, and in turn, the white blood cells identified as the B-lymphocytes convert into cells. The cells produce antibodies that help the body to fight the virus. The B-lymphocytes enable an infected individual to acquire life-long immunity even if they contract a contagious infection such as measles. However, HIV overturns this process in various ways, enabling the virus to hide from an individuals immune system. One of the main ways that HIV overturns the process is by killing and disabling the cells that strengthen ones defensive system.

Sequence Diversity and Immense Viral Clade

HIV-1 is one of the most diversified infections globally, making it difficult for researchers to analyze its characteristics. The HIV-1 M group has differentiated into nine different and divergent glades because it is driven by a reverse transcriptase (RNA) which tends to be subject to complex errors. The error-prone reverse transcriptase (RNA) has resulted in HIV-1 M group modification into multiple circulating recombinant forms. The most significant importance of Amino Acid sequences of Env is to diverge up to 25% within a particular clade and 40% between various clades. A vaccine immunogen will have to cope with the high virus diversity. The protection of the vaccine will therefore be greatly dependent on the ability of immune responses to cross-react with autologous viruses. Protective effectiveness will reduce substantially with an increased divergence between the vaccine, the vaccine divergence, and the infecting viruses.

The world population is also comprised of diversified individuals who portray different characteristics of HIV-1 infection in their bodies. For example, most individuals living in Europe portray different health characteristics from those living on the African continent. This can be attributed to the difference in lifestyle and the geographical weather conditions to which they are exposed. This aspect has significantly resulted in an increased viral sequence diversity from the different populations globally. Individuals from different geographical positions portray the difference in the viral proteins, which are majorly used during the research. Animal models used in the research for the HIV-1 vaccine also have different viral proteins because of the difference in geographical locations. The diversity and immense viral clade among human beings and animal models have made it difficult for researchers to come up with reliable conclusions during the research.

Hidden Viral Reservoirs

The most significant step that the healthcare researchers have undertaken toward the development of the HIV-1 vaccine development is manufacturing high effective anti-HIV drugs. Anti-HIV drugs are utilized in the treatment process for individuals who the virus has infected through a highly active antiretroviral therapy which helps in suppressing the replication of HIV (Vanhamel et al., 2019). However, HIV-1 continues to exist as a stably integrated and replication-component provirus in a heterogeneous strand of cells referred to as latent reservoirs in all infected individuals (Vanhamel et al., 2019). The reactivation of the latent reservoirs is the main cause of the recovery of the viruses in individuals undergoing the therapy. The reactivation and persistence of the latent reservoirs remain among the most challenging aspects of developing the vaccine for HIV-1 (Vanhamel et al., 2019). This is because the Latent HIV-1 reservoirs are mostly established during the early stages of an individuals infection before they appear and replicate in an individuals immune system.

Lack of Clarity in Immune Correlates of Protection

Vaccine protection for human beings against unwanted pathogens within the human system is only successful when there are positive responses from an individuals innate immunity. Lack of clarity in immune correlates of protection has also proved to be a challenge in the identification and development of HIV-1 vaccines (Tomaras & Plotkin, 2017). This is because the patients do not have the capacity to eliminate the virus from their system through humoral immunity. Researchers can only acquire reliable evidence regarding immune correlates of protection in the study of nonhuman primates and individuals who have been infected by HIV-1 (Tomaras & Plotkin, 2017). The researchers have outlined that nonhuman primates and HIV-1 positive individuals have the ability to spontaneously control viral replication to a lesser level (Tomaras & Plotkin, 2017). The medical practitioners have outlined that the desired results regarding immune correlates of protection can be obtained if studied on human beings.

Lack of Pharmaceuticals Interests

To obtain the most reliable results regarding the research on the development of the HIV-1 vaccine, it is appropriate for the medical practitioners to work together. This will entail pulling up resources and ideas into one pool (Nguni et al., 2020). When professionals work together, the probability of finding a solution is made possible and faster. However, many pharmaceuticals have lost interest in trying to find a vaccine for HIV-1 because of the complexities involved in the research processes. Negative comments from the pharmaceutical specialist about the impossibility of developing the vaccine have also discouraged other individuals interested in venturing into the activity (Nguni et al., 2020). Most owners of pharmaceutical factories have also abandoned the exercise due to the expensive nature of the activity since they invest a significant number of resources towards the exercise and end up recording losses (Nguni et al., 2020). The setbacks and disappointments are the main reason why most pharmaceuticals have lost interest in trying to conduct more research on the vaccine.

Small Animal Models

Medical research processes require the use of samples, making it easier for the researchers to be certain of the processes they are undertaking. Samples can be used to test the effectiveness of a given final output from the various vaccine development processes (Nguni et al., 2020). The efficacy of the developed medicines can only be determined by using human beings and other animals, such as nonhuman primates (Nguni et al., 2020). However, the research institutions have outlined a great risk in using human beings as the test models for the developed testing vaccines. This is because most of them are not certain of the impacts and side effects of the test vaccines on human health (Nguni et al., 2020). Other human rights organizations have also termed the use of human beings as test models to be a dehumanizing act that should not be advocated for. The researchers have resorted to using animal models such as chimpanzees, considered the most reliable animal models (Nguni et al., 2020). However, there has been a problem with the availability of animal models for vaccine effectiveness testing, which is also a major challenge in developing the HIV-1 vaccine.

Weakened Viruses for Human Utilization

Most medical researchers who develop vaccines for various infections utilize weakened or dead pathogens to manufacture vaccines to fight and stop the mutation of various viruses. Inactivated viruses are obtained by destroying the virulence of the virus, which makes them weak or kills them (Nguni et al., 2020). The viruses are majorly made inactive by the utilization of chemical alterations and being subjected to extreme heat to the point of being unable to invade and affect an individuals cells. When a virus is weakened or killed, it implies that the protein structure of the virus is significantly altered, which makes it impossible for them to protect the live proteins when utilized as a vaccine (Nguni et al., 2020). For an inactivated viral vaccine to be effective, it should portray its strong immune response to its live counterparts. Some of the inactivated viral vaccines have proven to be ineffective and hence require one to get a booster to acquire a long-term immunity (Nguni et al., 2020). Not all human beings immune systems are susceptible to inactivated virus vaccines; hence a challenge for the researchers to develop HIV-1 vaccines using the same procedures.

Broadly Reactive Neutralizing Antibodies Research Methods

Neutralizing antibodies (NAbs) are majorly used for treatment, prevention, and control of the spread of a given infection within an individuals immune system. The NAbs main function is to act antivirally on the highly preserved surface of the HIV envelope (Burton & Hangartner, 2019). The HIV-1 surfaces contain spikes, making it difficult for the neutralizing antibodies to access them. The broadly NAbs have captured the attention of most scientists due to their ability to neutralize very strong pathogens that have intruded into the human immune system (Burton & Hangartner, 2019). Studying them and having a great understanding of their functions will give the scientists a clear understanding of how to deal with strong pathogens.

However, obtaining the broadly reactive NAbs has also proven to be futile because there are no reliable methods to be used by the researchers to acquire the antibodies. The functions are only possible if the neutralizing antibodies have been used to design the vaccine for a given virus (Haynes et al., 2019). HIV-1 has proven to be the most difficult virus to deal with in the history of vaccine development in the health sector. This is because of the lack of a reliable method to acquire broadly reactive NAbs, which significantly helps in designing the most reliable vaccine for the virus (Burton & Hangartner, 2019). The scientists conducting the research have noted that the lack of NAbs is also one of the challenges hindering the development of the HIV vaccine.

Viral Evasion of Humoral and Cellular Immune Responses

HIV-1 is one of the strongest viruses and has the ability to evade humoral and cellular immune responses due to its strong nature. They are able to detect pattern recognition receptors, an individuals antibodies, and the T cell receptor, which are responsible for communicating to the immune system by modifying the receptors ligands (Nguni et al., 2020). The HIV-1 Nef protein has the capacity to protect all the infected primary cells from getting destroyed by the strong cytotoxic T-lymphocytes. The HIV-1 Nef proteins also destroy the antigen presentation process on the surface of the cells by creating resistance on the normal pathways to the major histocompatibility complex class 1 (MHC-1) (Nguni et al., 2020). This results in the weakness of the cytotoxic T-lymphocytes, making them unable to recognize the infected cells in the immune system. The ability of the virus to easily evade humoral and cellular immune responses has greatly contributed to the setbacks related to the study of the virus behavior (Nguni et al., 2020). This has made it difficult for the researchers to acquire reliable information for them to develop the vaccine.

Lack of Natural Protective Immune Responses

Natural remedies for various conditions are the most recommended due to their user-friendly nature in conducting research. These remedies are effective since they are easily accessible. Medical practitioners and pharmaceutical organizations have advocated for the use of naturally developed vaccines because they have negative side effects on an individuals immune system (Nguni et al., 2020). Traditionally, most individuals used different natural remedies as intervention plans for different infections. With the great advancements in the levels of technology in the health and science sector, highly reliable vaccines for different infections and diseases were developed using the available natural products (Nguni et al., 2020). Malaria is one of the diseases that had its vaccine developed from natural resources.

Upon the outbreak of HIV-1, most healthcare organizations were certain that the vaccine of the virus would eventually be acquired from a natural source. However, the vaccine for the virus has proven unavailable within natural settings (Nguni et al., 2020). Most individuals who have contracted different diseases have been able to battle such ailments naturally because of their bodys strong immune system. However, HIV-1 does not have a natural immune response against the disease because of its strong nature (Nguni et al., 2020). Natural remedies for the virus have also not been identified, making it difficult for the researchers to use them for the research. The lack of a natural protective immune response against the virus has also demoralized most scientists and researchers who fear that they may also get infected while trying to develop a remedy for the disease.

Antibody Responses

When any virus or antigen attacks an individuals body, the body releases antibodies that are capable of fighting the disease or the virus. An individuals immunity to a given viral infection is brought about by variously specific and non-specific mechanisms (Nguni et al., 2020). The interaction between the virus and the host cell plays a significant role in determining the immune functions, the magnitude, and the duration of the immune response. Individual antibody molecule within an individuals immune system is designed in a unique way to deal with and protect the body from a given pathogen (Nguni et al., 2020). The human immune system is unable to protect the body from HIV-1 infection because it does not have a specific antibody designated to prevent the mutation of the virus in an individuals system (Nguni et al., 2020). This has made it challenging for the researchers to identify the characteristics of an antibody that may be used to prevent the replication of HIV-1 in the early stages of an infection.

Conclusion

Millions of people worldwide continue living with HIV-1 and taking medications and therapies based on antiretroviral medications to prolong their lives. Most scientists have faced various challenges which have hindered them from eliciting durable and protective immune responses against HIV-1. Even though the researchers have not been able to determine the neutralizing antibody for HIV-1, a great advancement is achieved through developing life-prolonging drugs and antiretroviral medicine. These methods help contain the negative impacts of the virus on the human body. However, there is still hope since some scientists and researchers have not given up on their hope of getting the HIV-1 vaccine in the future. Tackling and finding solutions to the barriers to developing an effective vaccine for HIV-1 will positively impact the establishment of the HIV-1 vaccine globally.

References

Burton, D. R., & Hangartner, L. (2019). Broadly neutralizing antibodies to HIV and their role in vaccine design. Annual Review of Immunology, 34(1), 635659. Web.

Haynes, B. F., Burton, D. R., & Mascola, J. R. (2019). Multiple roles for HIV broadly neutralizing antibodies. Science Translational Medicine, 11(516). Web.

Nguni, T., Chasara, C., & Ndhlovu, Z. M. (2020). Major scientific hurdles in HIV vaccine development: Historical perspective and future directions. Frontiers in Immunology, 11. Web.

Tomaras, G. D., & Plotkin, S. A. (2017). Complex immune correlates of protection in HIV-1 vaccine efficacy trials. Immunological Reviews, 275(1), 245261. Web.

Vanhamel, J., Bruggemans, A., & Debyser, Z. (2019). Establishment of latent HIV-1 reservoirs: What do we really know? Journal of Virus Eradication, 5(1), 39. Web.

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