Progress of Vaccine Development, Particularly the Challenges.

¶ … progress of vaccine development, particularly the challenges. There is also a discussion of funding and its impact on HIV research.

Ever since HIV / AIDS made the evolutionary jump from chimpanzees to humans, it has infected approximately one percent of the global population; in 2005 it killed almost three million people alone. HIV's continued spread is due to its ability to evade the human immune system and vaccines (Understanding Evolution, 2007).

Even with recent advances in scientists' understanding of HIV origination, development and immunology, there are still major scientific obstacles. Several prototype HIV vaccine candidates have failed so far to protect against HIV infection or to reduce viral loads, that is, the concentration of HIV virus in the blood after infection during clinical studies of effectiveness. Therefore there must be a renewed, well-coordinated commitment to conducting basic discovery research as well as preclinical studies and clinical trials (Barouch, 2008).

In the nearly 30 years since HIV was identified as the agent that causes AIDS, more than 60 million people worldwide have been infected with HIV. Most of these individuals live in the developing world and nearly half of them have died. The ideal solution would be the development of a safe and effective HIV vaccine to control the worldwide AIDS pandemic, but HIV vaccine development efforts have been largely unsuccessful so far. According to Dan Barouch (2008) of the Harvard Medical School, this lack of success is due to the "extraordinary diversity of HIV-1, the capacity of the virus to evade adaptive immune responses, the inability to induce broadly reactive antibody responses, the early establishment of latent viral reservoirs, and the lack of clear immune correlates of protection…"

The goal of developing an HIV vaccine is to either prevent infection, or to reduce the concentration of HIV virus in the blood after infection, or to lessen clinical disease progression after infection. The ideal vaccine would completely block infection as well as provide sterilizing immunity. However, most clinically licensed vaccines do not do all these things. A more realistic goal would be the development of a less than ideal HIV vaccine that fails to prevent infection, but provides partial immune control of viral replication or reproducing after infection. Such partial control, shown by a reduction in peak and setpoint viral loads following infection, has been demonstrated in certain preclinical studies by vaccines that cause T. lymphocyte responses. Given that viral loads are the primary factor in HIV transmission, it is possible that a partially protective vaccine could have a significant impact on a population level (Barouch, 2008). In spite of the urgency, only two vaccine concepts had completed clinical efficacy studies as of 2008. Results of those studies highlighted new scientific challenges and led to significant debate regarding the optimal path forward for the field of HIV vaccine.

HIV vaccine strategies can be divided into two categories, traditional and novel approaches. Traditional vaccine technologies include the use of live attenuated viruses, whole killed viruses and protein subunits. Live attenuated viruses are not likely to be used in humans because of significant safety concerns, while whole killed have shown limited ability to produce reactive responses. Novel vaccine strategies include gene delivery technologies such as plasmid vaccines and live recombinant vectors. Both types of novel strategies are undergoing further evaluation (Barouch, 2008).

Developing a successful HIV vaccine requires that this field be able to attract and keep talented new investigators. Increased support for fellows and junior faculty should be considered a top priority for both senior investigators and funding organizations. Continued participation by industry is also necessary, since biotechnology and pharmaceutical companies have important capabilities that academic, government and non-profit organizations do not (Barouch, 2008).

More recent developments in 2010 included the demonstration of modest protection against HIV infection in humans through immunization, using a vaccine regimen including canary-pox-vector prime plus a protein-subunit boost in the RV144 trial in Thailand. Such news is encouraging given that for every two patients who begin receiving HIV treatment, there are five people who are newly infected (Koff & Berkley, 2010).

The Vaccine Research Center announced that a team of scientists discovered two potent human antibodies, VRC01 and VRC02, which can stop more than 90% of known global HIV strains from infecting human cells in the laboratory. These antibodies could be used to design better HIV vaccines or they could be further developed to prevent or treat HIV infection (National Institutes of Health, 2010).

Funding for HIV research also plays a critical role in developing a vaccine. Until 2008, funding for research and treatment in low- and middle-income countries grew rapidly, jumping to $20 billion in 2007 alone. The largest funder of basic research, the U.S. National Institutes of Health, doubled its budget to almost U.S.$3 billion. Science magazine correspondent Jon Cohen investigated how research dollars have been divided up, what they have achieved, how the money is accounted for and what happens in cases of abuse (Roberts & Jasny, 2008).

Cohen's investigation showed that a number of factors were responsible for the surge in HIV / AIDS funding that occurred through 2007, but the success with anti-HIV drugs was the most significant. For example, studies in Thailand and Uganda had shown by the late 1990s that effective and cheaper ways to prevent mother-to-child transmission with anti-HIV drugs had been developed. Following the 2000 international AIDS conference in Durban, South Africa, the issue of universal access increased HIV awareness to the point that billions of dollars from new sources began flowing into poor countries. In 2006 the UN General Assembly declared that every HIV-infected person who needed treatment should receive it by 2010. Global response to this declaration transformed the way that the developed world partnered with the developing world to address catastrophic health crises. As a result, HIV-infected people around the globe are now living longer; some communities have even seen their epidemics start to decline. Serious problems continue however, including the problem with several "donor darlings" receiving the majority of aid money while politically troubled countries receive little help. Other questions are still unresolved, such as how sustainable is the massive treatment rollout that has been under way (Cohen, 2008).

Global recession has also affected HIV vaccine development. Reports released in November 2011 showed that AIDS-related funding by European and U.S. donors dropped by 7%, or U.S.$44 million, to U.S.$612 million in 2010. The reports also showed that the number of donors giving more than U.S.$300,000 to HIV dropped by 30% over the past three years. Likewise, funding from donor governments also dropped in 2010. UNAIDS, the Joint United Nations Programme on HIV / AIDS, estimated that there will be at least an annual gap of U.S.$6 billion. UNAIDS also estimated that 12.2 million new HIV infections and 7.4 million HIV-related deaths could be avoided between 2011 and 2020 if funding could be increased up to U.S.$24 billion by 2015. UNAIDS Deputy Director Paul De Lay sums up the need for further investment and research: "Investing strategically today will not only save lives, it will also ultimately result in significant cost savings in the future" (UNAIDS, 2011).