The data from this study make important contributions to our

The data from this study make important contributions to our knowledge of immune responses to Zika virus and to the development of effective vaccines against Zika. The authors utilized purified E protein, which was characterized by low protein yields, indicating that prM protein may be required for optimal stability and that prM-E may be a more effective antigen. The effect of E protein trimerization was not specifically evaluated in this study and may serve as another useful technique to enhance protein production, stability, and immunogenicity. A large percentage of the human population possesses Ad5-specific antibodies, thereby limiting the usefulness of Ad5.ZIKV-Efl vaccine in humans. Nevertheless, the Ad5.ZIKV-Efl vaccine data are impressive and clearly demonstrate the robust immunogenicity of this platform, especially in light of the previously cited report () using rhesus adenovirus vector for which this complication is minimized. The MNA-ZIKV-rEfl vaccine data is less impressive but potentially of greater value. The MNA-vaccine platform has multiple production advantages: reproducibility, low cost and ease of manufacturing, product stability, the potential to require lower doses of antigen, simplified and painless vaccination procedure, the possible elimination of the cold chain storage needs. The system is amenable to the introduction of adjuvants that can be lyophilized and encapsulated in the microneedle array (i.e., TLR ligands or cytokines). The goals of this study and the model system used to evaluate protection are important in light of the impact of Zika infection on the developing fetus. Future work evaluating these vaccines in additional animal models (e.g., A129, AG129, SJL mice) may provide important additional information regarding these two vaccine platforms. A number of knowledge gaps concerning Zika virus still exist, posing questions that need to be answered in order to fully control this disease (). These gaps include: the How, Why, and When of Zika outbreaks, the risk factors for different clinical disease, the effects of co-infections with other arboviruses, details about transmission routes, the timing of risk during pregnancy, how age, immunocompetence, race, gender, and ion channels effect disease susceptibility or clinical outcome, the development of safety and efficacy data in pregnant women, the degree of cross-reactivity of vaccine strains, the development of appropriate animal models accurately reflecting human disease, and the establishment of correlates of protection in humans to name a few. Fortunately, the global health community has come together to combat this global problem. The provision of adequate resources in terms of funding, infrastructure, manpower, and long-lived commitment to the goal on the part of government, private industry, academia and other organizations will be essential if we are to eventually control this disease. Disclosure Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity after mumps vaccination (MISP Grant # 53375). This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is conducted in compliance with Mayo Clinic Conflict of Interest policies.
Antiretroviral therapy (ART) is among the greatest successes of modern medicine. The vast majority of patients taking ART will successfully control HIV replication, with the subsequent immunological recovery and an uneventful clinical course in most patients. Moreover, safety of the new drugs currently in use has been improved so that discontinuations due to adverse events have been minimized. Many studies suggest now that the lifespan of HIV-infected persons on ART might equal that of the non-HIV infected population. Only an excess morbidity and mortality associated to the development of the so-called non-AIDS events remains as a significant clinical problem (). It has been well demonstrated that non-AIDS events, including cardiovascular disease, non-AIDS cancers, osteoporosis, liver failure, renal failure, neurocognitive impairment, and frailty, as well as overall-mortality in HIV-infected patients on otherwise successful ART are related with persistent inflammation and immune activation (). The ultimate cause of this residual inflammation is not well understood, but persistent HIV-replication, bacterial translocation, aging, lifestyle factors, and coinfections, among others, have been advocated as contributors (). Since the relationship between inflammation and non-AIDS morbidity and mortality was established, there have been multiple attempts to find strategies that could help improve the situation. As the direct impact of any strategy on clinical endpoints requires large numbers of patients and long follow-up, most clinical trials and studies have evaluated the impact on markers of inflammation/immune activation previously shown to be associated with clinical outcomes. Early initiation of ART has been associated with a significant decrease in the number of non-AIDS events in a large clinical trial (), but no other studies with different strategies have offered similar results.