Development of HIV Vaccine

A review of the possible role of nanoparticles in the development of HIV vaccines

Praveen Gupta et al

Human Immunodeficiency Virus (HIV) has been the deadliest disease of twenty first century; it has turned into a global epidemic challenging even the most modern medical technology. HIV primarily infects vital cells in the human immune system such as helper T cells (specifically CD4+ T cells), macrophages and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: firstly, direct viral killing of infected cells; secondly, increased rates of apoptosis in infected cells; and thirdly, killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections. If untreated, eventually most HIV-infected individuals develop AIDS (Acquired Immunodeficiency Syndrome) and die. HIV infection has joined the list of diseases such as malaria against which we do not have any vaccines.

Well, there are some problems due to which the vaccine development has been unsuccessful:

The error prone mechanism of reverse transcription allows for the mutation of HIV and as a result, the virus escapes from the control by cytotoxic lymphocytes. It is also difficult to induce neutralising antibodies which have cross-clade activities. There have also been some concerns that antibodies may enhance HIV infectivity. Vaccine design for sometime has depended on discovery that attenuated and inactivated microorganisms can induce specific and protective immunity. But it is difficult to extend this strategy to AIDS because such vaccines suffer from drawbacks such as they are:

• difficult to produce
• potentially unsafe
• poorly immunogenic.

Based on this we have 2 major lessons to learn:

• Effective control of HIV is by cytotoxic lymphocytes
• This control would only be effective if controlled early so that the number of mutants produced are low

This means that the vaccine that is given must induce Th1 type of immune response, which can activate the cytotoxic T lymphocytes and that the efficacy must be at the mucosal sites, before the infection spreads systemically.

One of the best means of inducing the Th1 type of immunity is to use nanoparticles. Nanoparticles are solid colloidal particles having a size of less than or equal to 1000nm which may be made up of active principle or in which active principle is dissolved, entrapped or encapsulated and/or to which the active principle is adsorbed or attached. It is the size of this delivery system, which makes them more efficient in certain drug therapy applications such as intracellular localisation of therapeutic agents. Nanoparticles are usually prepared by the controlled precipitation of the polymer solubilised in one of the phases of the emulsion. Precipitation of the polymer out of the solvent takes place on solvent evaporation, salt addition or addition of an incompatible polymer leaving particles of the polymer suspended in the residual solvent. Polymeric nanoparticles comprise of biodegradable polymers and prove useful for antigen based vaccines due to their capacity of high antigen loading and enhanced antigen presentation efficiency. Synthetic polymers such as polycyanoacrylate and natural polymers such as chitosan or gelatin can be used to make nanoparticles. Antigen loading into particles can be achieved by two methods: by incorporating the antigen at the time of particle production or by adsorbing the antigen after the formation of particles by incubation in the drug solution. Increased MHC I antigen presentation can be achieved by priming Antigen Presenting Cells (APC) with antigen-encapsulating, acid-degradable nanoparticles, which degrade in the acidic environment of the endosome following phagocytosis, thus releasing the antigen into the cytoplasm. This is the first step towards the development of Th1 immunity. It is now known that the size and the composition of the nanoparticles determines its propensity to induce Th1 type of immunity. Several research groups are working to delineate the mechanisms by which nanoparticles can induce Th1 immunity.

Secondly, it is important that the infection be controlled at the first site of infection. Thus, the antigen encapsulated in nanoparticles must induce immunity at the mucosal site, which can be achieved by delivery of the antigen to the vaginal mucosa. Several scientists working with this believe that this strategy may lead to an effective vaccine against HIV.

With the integration of all the frontier technologies of 21st century i.e. nanotechnology and biotechnology we can conquer the unconquerable. Use of nanoparticles eliciting an immune response for HIV through antigen presentation is being studied upon and there have been lot of independent researches using nanoparticles to initiate an immune response and many have been successful. Nanobiotechnology has provided us with a ray hope in the darker times of global pandemics such as HIV, H5N1, ebola and lot of other viruses that threaten to take over the human race.

(Praveen Gupta, Ashish Deo, Swati Khandelwal, Aditi Nagardeolekar and Aditya Pattani are associated with H(S)NCB's College of Pharmacy)