Immunology and the Quest for an HIV Vaccine

It has been almost three decades since the first report of AIDS came to light. Of course, we now estimate that HIV/AIDS had been around for approximately 50 years, two decades before it was noticed in the United States (US) in 1981, but the the earliest account of HIV-1 may have found in 1959 in Congo (now Democratic Republic of Congo, or DRC). When the first announcement of an HIV discovery was made in 1983, it was widely expected that we would have a vaccine within a very short time. But, after so many years, it is sad to admit that our understanding of immunity against retroviruses is limited.We are trapped in the tunnel vision of the classical immunity paradigm, where we are trying to develop a vaccine by eliciting antibodies to the HIV-1 envelope or cell-mediated immunity to HIV-1 antigens. Thus far, we have been unable to see anything beyond the limited boundaries of that paradigm. There are substantial amounts of data emerging from the well regarded laboratories in the US, Canada, and Europe that strongly suggest that anti-HIV-1 neutrilizing antibodies and CMI immunity (both part of the classical immunity) have no significant positive effects in quelling HIV-1. Data from SIV-infected natural hosts show that disease progression is averted in the presence of relatively high levels of viral replication and detectable, although low, classical immune responses (6). It is time to shift our focus towards other immunities that are operational in Homo sapiens, and all other life forms. It should be realized that HIV-1 is a retrovirus, and adaptive immunity or innate immunity-based vaccines are not the solution, but may be the major problem. How do life forms protect themselves against retroelements and retroviruses? Obviously, protective immunity against retroelements is different than what we are currently focused on. We must look at an immune system that is not based on classical or adaptive immunity.

In our experience, the transitions from an existing paradigm to the new ones have never been easy or painless— but in many ways, HIV vaccinology is on the cusp of such a period of transition, along with much of cell biology and biomedicine. It all has to do with a growing new understanding of the functions of small double-stranded (ds) RNA and of related epigenetic phenomena known as RNA-interference and microRNAs, which may ultimately prove to be as profound and far-reaching as was the development of recombinant DNA technology over four decades ago. Perhaps this new understanding will even come to rank with the discovery of the structure of DNA itself over five decades ago—yet this new approach lends itself to much more practical application and engineered solutions than the earlier theoretical work ever did.