HIV 1-C Characterization Studies
In order to facilitate vaccine development, researchers at HAI are conducting in-depth genetic analysis of HIV-1C. To explain why subtype C has been spreading faster throughout southern Africa, researchers are working to characterize its molecular and biologic traits. Researchers within the laboratories are investigating particular parts or sections of subtype C’s genome as well as the virus as a whole.

Because HAI researchers have developed an infectious clone of subtype C, the first infectious molecular clone of HIV-1C from an isolate in Africa, they are now able to introduce mutations to the genome and examine changes in the biologic activity, such as the ability to infect different types of cells. This development is critical in the development of new vaccine strategies.

Genomic Analysis of HIV 1-C
As researchers continue to develop new interventions and strategies for preventing mother-to-infant transmission of HIV, studies are underway to determine the genetic characteristics of the virus that has been transmitted among mother-infant pairs in Botswana. By comparing virus isolated from infants with virus isolated from samples of blood, breast milk, and cervicovaginal fluid, researchers aim to identify what route is most involved in the transmission of the virus from mother to infant. Defining the particular characteristics of HIV-1C’s genome that improve its ability to be transmitted. and cause disease, will allow researchers to evaluate the efficiency of current interventions and design new approaches to protect the health of infants and adults.

At HAI, researchers are also investigating genomic differences in the different HIV viral forms circulating in Tanzania. Researchers have examined different recombination patterns among HIV-1 subtypes A and C between mothers and infants, and, in the process, have identified a new circulating recombinant form (CRF) of the HIV virus. Through a study of nearly 1,000 HIV-infected women living in Tanzania, researchers discovered that subtype C and certain recombinants—hybrids of different subtypes—may be transmitted more effectively from mothers to infants than other subtypes. It is anticipated that this study will yield valuable information on preventing the infection of children through breastfeeding.

Cytotoxic T Lymphocytes (CTL) Study
The CTL study seeks to identify regions of the HIV-1C genome that are considered critical to the design of a vaccine that would be most effective within southern Africa. Researchers have identified and characterized profiles of CTL epitopes, proteins on the cell surface that bind with antibody or cells. These proteins have the ability to kill virus-infected cells and are key to the body’s immune response to control HIV infection. The researchers will use the CTL epitopes or CTL epitope-rich regions found to enhance the immune system’s ability to attack infected cells in vaccine designs underway at HAI.

By analyzing the cumulative HIV-1C specific CTL responses of HIV-infected donors in Botswana, preliminary results have indicated that the characteristics of the virus that cause the HIV-1 epidemic in a certain geographic area and the genetic background of the population might affect the CTL responses in individuals receiving the vaccine.

In a linked investigation, researchers are also analyzing particular types of antigens known as HLA types that restrict CTL responses. Understanding common HLA types is important to vaccine design as immune response might be influenced by a particular HLA type. Researchers are looking for the most common HLA types in Botswana in order to design the best vaccine against HIV.