In conclusion, in this study we found a high mortality rate in TB patients requiring intensive care, especially in those with an early ICU admission. Nevertheless, additional studies are necessary to confirm this data, taking into account other possible risk factors for mortality like MDR-TB and low serum levels of antituberculosis drugs, potentially improving the care of critically ill TB patients. Comparative Efficacy of Hemagglutinin, Nucleoprotein, and Matrix 2 Protein Gene-Based Vaccination against H5N1 Influenza in Mouse and Ferret Efforts to develop a broadly protective vaccine against the highly pathogenic avian influenza A (HPAI) H5N1 virus have focused on highly conserved influenza gene products. The viral nucleoprotein (NP) and ion channel matrix protein (M2) are highly conserved among different strains and various influenza A subtypes. Here, we investigate the relative efficacy of NP and M2 compared to HA in protecting against HPAI H5N1 virus. In mice, previous studies have shown that vaccination with NP and M2 in recombinant DNA and/or adenovirus vectors or with adjuvants confers protection against lethal challenge in the absence of HA. However, we find that the protective efficacy of NP and M2 diminishes as the virulence and dose of the challenge virus are increased. To explore this question in a model relevant to human disease, ferrets were immunized with DNA/rAd5 vaccines encoding NP, M2, HA, NP+M2 or HA+NP+M2. Only HA or HA+NP+M2 vaccination conferred protection against a stringent virus challenge. Therefore, while gene-based vaccination with NP and M2 may provide moderate levels of protection against low challenge doses, it is insufficient to confer protective immunity against high challenge doses of H5N1 in ferrets. These immunogens may require combinatorial vaccination with HA, which confers protection even against very high doses of lethal viral challenge. Since 1997, the highly pathogenic avian influenza A H5N1 viral strain has caused severe disease in poultry and wild birds. Although H5N1 has not spread widely in humans, sporadic infections have been seen throughout countries of eastern Asia, the Middle East and Africa. To date, there have been more than 445 confirmed human cases of H5N1, with 263 deaths (59% mortality rate) reported by the World Health Organization (http://www.who.int/csr/disease/ avian_influenza/country/cases_table_2009_12_11/en/index.html). In almost all cases, those infected with H5N1 had physical contact with infected birds. While the primary mode of transmission may be animal-to-human, the concern remains that this virus may evolve into a strain capable of human-to-human transmission. Vaccination offers a practical and effective measure for controlling the spread of this highly pathogenic virus. The threat posed by emerging strains of influenza is unpredictable and varies among countries, as evidenced by the recent swine origin H1N1 pandemic, highlighting the need for improved vaccines that can confer broad protection against multiple viral strains and various influenza A subtypes.