Although HER2/neu-targeted cancer vaccines have shown initial promise in the adjuvant setting, a therapeutic vaccine remains elusive due to the tumor escape mechanisms of established cancer. As described by Seavey et al. in this issue of CCR, a Listeria-delivered vaccine may help overcome immune tolerance, leading to an effective therapeutic vaccine.

Generation of a therapeutic immune response against a diverse set of antigens expressed by a patient’s cancer is a central goal of cancer immunotherapy. This goal is important because diverse responses may prevent escape of antigen loss variants. To accomplish this goal we have developed tumor-derived autophagosome-enriched vaccines, “DRibbles”, that sequester a complex mixture of proteins incl...

The kinetics of immune escape and reversion depend upon the efficiency of CD8 cytotoxic T lymphocytes (CTL) and the fitness cost of escape mutations. Escape kinetics of three simian immunodeficiency virus Gag CTL epitopes in pigtail macaques were variable; those of KP9 and AF9 were faster than those of KW9. Kinetics of reversion of escape mutant virus to wild type upon passage to naïve major hi...

Host immunosurveillance as a mechanism to promote tumor growth or to suppress tumor development is well studied. It is less known how immuno-selective pressure in the form of immunotherapies can instruct the immune system during this process. We hypothesized that the application of a T cell-dependent selection pressure in the form of a whole tumor vaccine would alter the immunogenic architectur...

V3-glycan-targeting broadly neutralizing antibodies (bNAbs) are a focus of HIV-1 vaccine development. Understanding the viral dynamics that stimulate the development of these antibodies can provide insights for immunogen design. We used a deep-sequencing approach, together with neutralization phenotyping, to investigate the rate and complexity of escape from V3-glycan-directed bNAbs compared to...

Hepatitis B virus (HBV) is responsible for a serious, potentially fatal disease that affects approximately two billion people worldwide. Although an extended HBV immunization program has run since 1991, representing the most effective preventive measure possible, leading to a dramatic reduction of HBV hepatitis incidence, 4.5 million new HBV infections still occur every year. In 1988 the emerge...

Broadly cross-neutralizing (BCN) antibodies are likely to be critical for an effective HIV vaccine. However, the ontogeny of such antibodies and their relationship with autologous viral evolution is unclear. Here, we characterized viral evolution in CAP256, a subtype C-infected individual who developed potent BCN antibodies targeting positions R166 and K169 in the V2 region. CAP256 was superinf...

CD8+ class I-restricted cytotoxic T lymphocytes (CTLs) usually incompletely suppress HIV-1 in vivo, and while analogous partial suppression induces antiretroviral drug-resistance mutations, epitope escape mutations are inconsistently observed. However, escape mutation depends on the net balance of selective pressure and mutational fitness costs, which are poorly understood and difficult to stud...

Under selective pressure from the host immune system, antigenic epitopes of influenza virus hemagglutinin (HA) have continually evolved to escape antibody recognition, termed antigenic drift. We analyzed the genomes of influenza A(H3N2) and A(H1N1)pdm09 virus strains circulating in Thailand between 2010 and 2014 and assessed how well the yearly vaccine strains recommended for the southern hemis...

Ligand-binding epitopes of proteins can mutate rapidly, as shown by viral mutations that lead to escape from neutralizing antibodies. We have undertaken to recreate in vitro the evolutionary competition between viral mutations that allow escape from antibody binding and host mutations that generate new neutralizing antibodies to the mutated viral antigen. To examine this vital race, we describe...