UCLA

Viruses have plagued humanity for thousands of years, but it is only in the last few centuries that we have even begun to develop vaccines and therapeutics to manage them. While we now have myriad vaccines that reduce death and suffering hugely compared to even half a century ago, millions of people still die every year from viral infections—some of which are preventable given current vaccines. Part of this is attributable to inequities that persist globally, but many deaths still result from diseases that we have been unable to control adequately. The main issues in producing effective vaccines derive from two factors: inability to induce an adequate immune response, and the ability of the pathogen to avoid an immune response. In many cases, such as HIV-1, certain flu strains, and hepatitis C virus, both are an issue. In HIV-1, a high tolerance for mutations allows for rapid escape from antibodies, which are adequate to prevent infection for many other pathogens. Conversely, we do not have methods to reliably generate T cell responses capable of broad recognition, and it is unknown whether doing so would even suffice. However, to approach more mechanistic explanations of how particular conditions affect an immune response, it is valuable to study the results of all vaccine trials, failed or otherwise. To this end, I characterize the antiviral capabilities of CD8+ cytotoxic T lymphocyte (CTL) clones that were elicited by the Mrk/Ad5 vaccine, a recombinant adenoviral vector that introduced single variants of the HIV-1 gag, pol, and nef genes. By testing their ability to kill and suppress virus-infected cells, I found that most clones were able to efficiently target the sequence used in the vaccine, but each exhibited very limited antiviral functions when tested against common epitope variants. The most recent pandemic, caused by SARS-CoV-2, has killed millions in a span of a few years, despite public health measures and rapid development of vaccines. A common issue seen in both SARS-CoV-2 vaccination and after infection is an apparent rapid waning of immune responses. As T cells are very important in containing and clearing most viral infections, it is crucial to characterize their responses in these contexts. By testing responses against SARS-CoV-2 structural proteins, I characterize the distribution of CTL targeting, the immunodominance of this targeting, and the persistence of different T cell responses elicited in either natural infection or SARS-CoV-2 mRNA vaccination.