The first human HIV-1 case, also referred to as simply HIV, was reported more than 30 years ago, which marked the start of a compelling campaign between the human race and this global pandemic. However, the battle was not optimistic and somewhat bleak and the production of a viable and efficient HIV-1 vaccine, if any, is still out of arms reach and rather distant. Nevertheless, several recent studies have suggested potential cues to untangle the complex mechanisms that are required to elicit immunogenic responses and generate a protection-level of neutralizing antibodies in the human body, which may shed some light on the potential development of an effective HIV-1 vaccination.

What Prevents Vaccine Development?

Currently, the majority of research on making a viable HIV-1 vaccine are focused on generating antigens that share either structural or epitope-level similarities with the surface envelope glycoprotein complex (Env) that mediates HIV-1 entry into host cells. Ideally, the antibodies generated by the immune response should be able to recognize and neutralize the Env complex, thus blocking the virus entry into human CD4 cells (T helper lymphocytes) and interrupting the HIV-1 infection process. However, the Env complex itself is a native trimer that protects itself from antibody neutralization by a combination of antigenic diversity, heavy glycolysation, and the presence of crucial epitopes deep within its quaternary structure. Moreover, extensive somatic hypermutation is required for antibodies to gain the ability to recognize the Env trimer and thus block HIV-1 infection at its early stage. The above reasons contribute to most of the obstacles that prevent an effective HIV-1 vaccine from being developed.

Discoveries

Recently, several laboratory studies have produced noticeable results and, if combined, may serve as important means of developing a potential HIV-1 vaccine. Firstly, Sanders et al. successfully produced a structurally similar trimer with immunogenic activities. Such a trimer can be used to immunize rats and monkeys to elicit the expression of protective antibodies that recognize the trimer itself. This study demonstrated the possibility of using a protein trimer as an immunogen i.e. an agent that will trigger an immune response. Secondly, Chen et al. successfully expressed the near-homologous native Env trimer in cultured cells. This contributed greatly to the practice of mass production of an Env trimer as an immunogen. Finally, investigations by Jardine et al. and Dosenovic et al. generated special genetically-engineered mice that, when immunized with a slightly-modified version of the Env trimer, were sufficient to generate lineage-specific B-cell lines that possess the potential of producing antibodies recognizing the trimer, although still not enough to reach the neutralizing level.

Solutions

These recent discoveries, while promising, reveal the high degree of integrity required for the development of an HIV-1 vaccine. It is clear that the production of an HIV-1 vaccine requires an extremely high level of organization and structure, as each research group is only highly specialized within their own field. From the perspective of investment strategists, two alternative solutions exist in parallel. The first solution, on one hand, is the whole R&D department be divided into several compartments and even outsourced, leaving a central hub to monitor the progress of each R&D unit as well as the coordination between units. The advantages of such organizational structure will include minimizing collateral risk and allowing several groups to work on the same research topic in parallel, thus increasing the chance of success. On the other hand, another solution is that investors consider bringing separate R&D units under the same roof, which would greatly facilitate interactions between individual research segments and increase efficiency.

Naturally, there may be a number of factors affecting the actual strategy implemented by the investors including company culture, management style, and free available resources. Nevertheless, the recent developments in the field of an HIV-1 vaccine provide potential investors and strategists a picture on this complex, yet promising industry.

References:

1. R. W. Sanders et al., Science 349, aac4223 (2015).

2. J. Chen et al., Science 349, 191 (2015).

3. J. G. Jardine et al., Science 349, 156 (2015).

4. P. Dosenovic et al., Cell 161, 1505 (2015).