HIV vaccine: Can it be developed in the 21st century?

Abstract

HIV infection is a major public health problem especially in the developing countries. Once a person infects with HIV, it remained infected for lifelong. The advanced stage developed after 10–15 y of HIV infection that stage is called acquired immunodeficiency syndrome (AIDS). From 1990 to 2000 the number of people living with HIV rose from 8 million to 27 million; since the beginning of the HIV/AIDS epidemic, AIDS has claimed almost 39million lives so far. Till now, there is no cure for HIV infection; however, after the introduction of effective treatment with antiretroviral (ARV) drugs the HIV individual can enjoy healthy and productive lives. Vaccine is safe and cost-effective to prevent illness, impairment, disability and death. Like other vaccines, a preventive HIV vaccine could help save millions of lives. All vaccines work the same way i.e. the antigen stimulate the immune system and develop antibodies. The ultimate goal is to develop a safe and effective vaccine that protects people worldwide from getting infected with HIV. However, some school of thought that vaccine may protects only some HIV people, it could have a major impact on the rates of transmission of HIV and this will help in control of epidemic, especially in populations where high rate of HIV transmission. In the past, some scientist doubted on the development of an effective polio vaccine, but now we are near to eradicate the polio from the world this is possible because of successful vaccination programmes. HIV vaccine research is aided by the not-for-profit International AIDS/HIV vaccine Initiative (IAVI), which helps to support and coordinate vaccine research, development, policy and advocacy around the world. Although the challenges for scientist are intimidating but scientists remain hopeful that they can develop safe and effective HIV vaccines for patients in future.

Human immunodeficiency virus (HIV) infection is a major public health problem particularly in low and middle income countries The HIV is a retrovirus that infects cells of the immune system of the body, destroying or impairing their function. Once a person infects with HIV, it remained infected for lifelong. As the infection progresses, the immune system becomes weaker, and the person becomes more susceptible to other infections. The advanced stage developed after 10–15 y of HIV infection that stage is called acquired immunodeficiency syndrome (AIDS). The route of transmission for HIV is unprotected sexual intercourse (anal or vaginal), transfusion of contaminated blood, sharing of contaminated needles, and mother to her infant during pregnancy, childbirth and breastfeeding.¹

From 1990 to 2000 the number of people living with HIV rose from 8 million to 27 million; since the beginning of the HIV/AIDS epidemic, AIDS has claimed almost 39million lives so far.² Globally, at the end of year 2014, 1.2 million (980000-1.6 million) people died from HIV and its related causes and 36.9 million (34.3 million-41.4 million) people were living with HIV/AIDS having 2 million (1.9 million -2.2 million) people becoming newly infected with HIV. Sub-Saharan Africa is the most affected region in the world having 24.7 [23.5–26.1] million people living with HIV. Also sub-Saharan Africa accounts almost 70% of the global new HIV infections. HIV infection is usually diagnosed by blood testing to detect presence or absence of HIV antibodies. Till now, there is no cure for HIV infection; however, after the introduction of effective treatment with antiretroviral (ARV) drugs the HIV individual can enjoy healthy and productive lives.³

Although, antiretroviral treatments have drastically improved life expectancy and quality of life for people living with HIV, but preventing HIV infection is still a primary goal for developing countries that are hardest hit by the pandemic and cannot afford treatments. Decades of effort have been spent, and continue to be made, toward developing an HIV vaccine. This particular virus, however, poses unique challenges to vaccine development. History shows that vaccines have been the most effective means to prevent and even eradicate some communicable diseases like small pox and polio. Vaccine is safe and cost-effective to prevent illness, impairment, disability and death. Like other vaccines, a preventive HIV vaccine could help save millions of lives. All vaccines work the same way i.e., the antigen stimulate the immune system and develop antibodies.

The ultimate goal is to develop a safe and effective vaccine that protects people worldwide from getting infected with HIV. However, some school of thought that vaccine may protects only some HIV people, it could have a major impact on the rates of transmission of HIV and this will help in control of epidemic, especially in populations where high rate of HIV transmission. The effective vaccine could decrease the number of people who get infected with HIV, further reducing the number of people who can pass the virus on to others. Developing safe, effective and affordable vaccines against HIV that can prevent HIV in uninfected people is the best hope for controlling the HIV epidemic especially in the developing countries and also a vaccine could be helpful for people living with HIV by slow down the progression of the disease and delay the onset of AIDS.

It is very difficult to develop vaccine against HIV/AIDS because HIV destroys the immune system of body, as soon as HIV enters into body, the virus inserts its genetic material into human cells, where the immune system of the body does not react, HIV has different subtypes, each of which is very different from the others, even within each subtype, HIV is highly variable and constantly changing, nobody has ever recovered in body from HIV infection and there is no natural mechanism to imitate. For vaccine experiment, the use of non human primate (NHP) models could become a more significant model as compared to animal models.⁴

In the past, some scientist doubted on the development of an effective polio vaccine, but now we are near to eradicate the polio from the world this is possible because of successful vaccination programmes. However, there are many reasons to be optimistic about the search for an HIV vaccine, despite the difficulties and the slow progress so far.

Development of vaccines against many diseases took many years to develop, however the HIV was only discovered in the mid-1980s. Currently, there are no approved preventive vaccines for HIV infection. Since the first HIV vaccine trial opened in 1987, researchers have studied more than 50 different preventive vaccine candidates in more than 100 National Institute of Allergy and Infectious Diseases (NIAID)- funded clinical trials. The world has very hope on the scientists, especially given the current speed of scientific progress on HIV vaccine. The main reason for hopeful is that most people of HIV remain healthy for several years after becoming infected with HIV. Few HIV people have survived as long as 20 y without developing AIDS, and also HIV never entirely rid from human body. Also, neutralizing antibodies have been detected among some of HIV patients and this suggests that the immune system can be quite effective at controlling HIV infection in the body. To test the safety and efficacy, the HIV vaccine must pass through 4 phases of clinical trials. The clinical trial phases usually last from 12 to 18 months, whereas the fourth phase can take 3 or 4 y to complete.

The clinical trial phase I involves few number of HIV-negative subjects to test the safety, phase II involves hundreds of subjects to further assess safety whereas phase III involves thousands of subjects are tested for safety and efficacy. It is important to test safety and efficacy among HIV infected i.e. to test HIV vaccine can delay disease progression or not. The Thai Phase III HIV vaccine clinical trial, also known as RV144, was the largest HIV vaccine study ever conducted and involved more than 16,000 volunteers in Thailand. This US. Army-sponsored study showed that an investigational HIV vaccine regimen was safe and modestly effective at reducing the rate of HIV infection; study participants who received the vaccine were 31.2 percent less likely to have become HIV-infected were placebo recipients.⁵

The Pox Protein Public-Private Partnership or P5 was established in 2010 to build on the results of RV144. The partnership, which is comprised of the NIAID, the Bill & Melinda Gates Foundation, the HIV Vaccine Trials Network (HVTN), the US. Military HIV Research Program, Sanofi Pasteur and Novartis Vaccines, seeks to advance and ultimately license HIV pox-protein vaccine candidates that have the potential to achieve a broad public health impact.⁵ This clinical trial of RV144 (the canarypox-based recombinant vaccine used as the prime), a recombinant candidates have also been developed based on adenovirus. A recent trial of RV 144 was halted in July 2013 because the trial had found that this vaccine failed to lower risk of infection in the recipients.⁶

Another clinical trial of simian immunodeficiency virus (SIV) vaccine in rhesus macaque monkeys gave the idea of using cytomegalovirus (CMV) as a prime in HIV vaccine development. The basis of SIV vaccine is that T cells known as killer T cells, which can kill infected cells, provide the protection afforded by the vaccine. The vaccine that stimulate the immune response in the mucosal surface of the gut at the same site where HIV replicate under trial. Ultimately, the goal of scientists is to explore the ways of generating antibodies to HIV and the roles of antibodies are able to neutralize viruses before they infect a person. The results of many trial in the last 2 y shows that some humans produce antibodies and capable of neutralizing a wide range of HIV strains. The production of antibodies against HIV strain highlighting weaknesses on the surface of HIV. HIV vaccine research is aided by the not-for-profit International AIDS/HIV vaccine Initiative (IAVI), which helps to support and coordinate vaccine research, development, policy and advocacy around the world. In addition, an alliance of organizations called the Global HIV/HIV vaccine enterprise exists to coordinate research and promote scientific cooperation and collaboration.⁷ Currently, about 30 NIAID -sponsored preventive HIV vaccine clinical trials are underway or planned for various stages of testing in the various part of world. In the next 2 years, more vaccines will be studied than in the last 5 y combined, and thousands of additional healthy volunteers from all populations will be needed in the coming years. Although the challenges for scientist are intimidating but scientists remain hopeful that they can develop safe and effective HIV vaccines for patients in future.

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.