UC Irvine Department of Medicine

[This corrects the article DOI: 10.1017/ash.2022.205.].

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus monkeys (Macaca mulatta) that lacked the protective MHC class I allele Mamu-A*01 (ref. 3). Here we show that an improved T-cell-based vaccine regimen using two serologically distinct adenovirus vectors afforded substantially improved protective efficacy in this challenge model. In particular, a heterologous rAd26 prime/rAd5 boost vaccine regimen expressing SIV Gag elicited cellular immune responses with augmented magnitude, breadth and polyfunctionality as compared with the homologous rAd5 regimen. After SIV(MAC251) challenge, monkeys vaccinated with the rAd26/rAd5 regimen showed a 1.4 log reduction of peak and a 2.4 log reduction of setpoint viral loads as well as decreased AIDS-related mortality as compared with control animals. These data demonstrate that durable partial immune control of a pathogenic SIV challenge for more than 500 days can be achieved by a T-cell-based vaccine in Mamu-A*01-negative rhesus monkeys in the absence of a homologous Env antigen. These findings have important implications for the development of next-generation T-cell-based vaccine candidates for HIV-1.

Non-communicable diseases, particularly cardiovascular diseases, are the leading cause of decreased life expectancy and death in Latin America and the Caribbean. Although a lifestyle, which includes no tobacco use, good nutrition, and regular physical activity is touted as key to health, the environmental, racial, social and economic conditions, which underpin lifestyle are often ignored or considered only secondarily. Placing the main responsibility on a patient to change their lifestyle or to simply comply with pharmacological treatment ignores the specific conditions in which the individual lives. Furthermore, there are major disparities in access to both healthy living conditions as well as access to medical care. There is sufficient evidence to support advocating for policies that support healthy living, particularly healthy food choices. Progress is being made to improve the food environment with enactment of front of package nutritional labels. However, policies were enacted only after intense regional research and advocacy supporting their implementation. Government officials must rise above the pressures of commercial interests and support health-promoting policies or be exposed as self-interest groups themselves. Strong advocacy is required to persuade officials that all policies should take health into consideration both to improve lives and economies.