Background A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety and immunogenicity of an HIV vaccine that combines a plasmid-DNA priming vaccine and a modified vaccinia virus Ankara (MVA) boosting vaccine. Methods Forty healthy volunteers were injected with DNA plasmids containing gp160 of HIV-1 subtypes A, B, and C; rev B; p17/p24 gag A and B, and RTmut B by use of a needle-free injection system. The vaccine was administered intradermally or intramuscularly, with or without recombinant granulocyte macrophage colony-stimulating factor, and boosted with a heterologous MVA containing env, gag, and pol of CRF01A_E. Immune responses were monitored with HIV-specific interferon (IFN)-γ and interleukin (IL)–2 ELISpot and lymphoproliferative assays (LPAs). Results Vaccine-related adverse events were mild and tolerable. After receipt of the DNA priming vaccine, 11 (30%) of 37 vaccinees had HIV-specific IFN-γ responses. After receipt of the MVA boosting vaccine, ELISpot assays showed that 34 (92%) of 37 vaccinees had HIV-specific IFN-γ responses, 32 (86%) to Gag and 24 (65%) to Env. IFN-γ production was detected in both the CD8+ T cell compartment (5 of 9 selected vaccinees) and the CD4+ T cell compartment (9 of 9). ELISpot results showed that 25 (68%) of 37 vaccinees had a positive IL-2 response and 35 (92%) of 38 had a positive LPA response. Of 38 subjects, a total of 37 (97%) were responders. One milligram of HIV-1 DNA administered intradermally was as effective as 4 mg administered intramuscularly in priming for the MVA boosting vaccine. Conclusion This HIV-DNA priming–MVA boosting approach is safe and highly immunogenic. Trials registration International Standard Randomised Controlled Trial number: ISRCTN32604572.

Administration of a multiple-dose series of M. vaccae to HIV-infected adults with childhood Bacille Calmette-Guérin immunization is safe and is associated with significant protection against definite tuberculosis. These results provide evidence that immunization with a whole cell mycobacterial vaccine is a viable strategy for the prevention of HIV-associated tuberculosis.

Clinical and subclinical tuberculosis are common among ambulatory HIV-infected persons, and some cases can only be identified by sputum culture. World Health Organization guidelines for screening for latent tuberculosis before treatment do not recommend sputum culture and, therefore, may fail to identify a substantial number of HIV-infected persons with subclinical, active tuberculosis.

Background We conducted a phase I/II randomized placebo-controlled trial with the aim of exploring whether priming with a low intradermal dose of a multiclade, multigene HIV-1 DNA vaccine could improve the immunogenicity of the same vaccine given intramuscularly prior to boosting with a heterologous HIV-1 MVA among healthy adults in Dar es Salaam, Tanzania. Methods Sixty HIV-uninfected volunteers were randomized to receive DNA plasmid vaccine 1 mg intradermally (id), n = 20, or 3.8 mg intramuscularly (im), n = 20, or placebo, n = 20, using a needle-free injection device. DNA plasmids encoding HIV-1 genes gp160 subtype A, B, C; rev B; p17/p24 gag A, B and Rtmut B were given at weeks 0, 4 and 12. Recombinant MVA (108 pfu) expressing HIV-1 Env, Gag, Pol of CRF01_AE or placebo was administered im at month 9 and 21. Results The vaccines were well tolerated. Two weeks after the third HIV-DNA injection, 22/38 (58%) vaccinees had IFN-γ ELISpot responses to Gag. Two weeks after the first HIV-MVA boost all 35 (100%) vaccinees responded to Gag and 31 (89%) to Env. Two to four weeks after the second HIV-MVA boost, 28/29 (97%) vaccinees had IFN-γ ELISpot responses, 27 (93%) to Gag and 23 (79%) to Env. The id-primed recipients had significantly higher responses to Env than im recipients. Intracellular cytokine staining for Gag-specific IFN-γ/IL-2 production showed both CD8+ and CD4+ T cell responses. All vaccinees had HIV-specific lymphoproliferative responses. All vaccinees reacted in diagnostic HIV serological tests and 26/29 (90%) had antibodies against gp160 after the second HIV-MVA boost. Furthermore, while all of 29 vaccinee sera were negative for neutralizing antibodies against clade B, C and CRF01 AE pseudoviruses in the TZM-bl neutralization assay, in a PBMC assay, the response rate ranged from 31% to 83% positives, depending upon the clade B or CRF01_AE virus tested. This vaccine approach is safe and highly immunogenic. Low dose, id HIV-DNA priming elicited higher and broader cell-mediated immune responses to Env after HIV-MVA boost compared to a higher HIV-DNA priming dose given im. Three HIV-DNA priming immunizations followed by two HIV-MVA boosts efficiently induced Env-antibody responses.

In June 2016, an outbreak of an unknown disease was reported to affect clusters of families in two regions of the central part of Tanzania. A rapid epidemiological survey was conducted in the affected villages, with a detailed house-to-house survey in selected households. A total of 68 cases occurred between 14 May and 14 November 2016, of which 20 died, making a case fatality rate of 30%. Over 50% of the cases were below the age of 15 years. The cases presented with jaundice (n=60), abdominal pain (n=59), vomiting (n=56), diarrhoea (n=34) and ascites (n=32). The responsible food item appeared to be home grown maize. The rate ratio indicated that the occurrence of illnesses was associated with ingestion of food contaminated with high levels of aflatoxins (contamination range: 10-51,100 μg/kg and 2.4-285 μg/kg for case and control households, respectively). Serum aflatoxin biomarker indicated that cases were more likely to have higher than 1000 pg/mg aflatoxin-albumin adduct level in their sera compared to controls (Odds Ratio = 13.5; 95% confidence intervals = 1.5-165.3; range of aflatoxin-albumin adduct level = 36- 32,800 pg/mg for cases and 10-4020 pg/mg for controls). Beside aflatoxins, maize samples were also contaminated with high levels of fumonisins (range of contamination; 945-12,630 μg/kg) with 8 of 10 samples analysed from case households co-contaminated with both toxins at levels above the maximum limit of 5 or 10 μg/kg set for AFB1 or total aflatoxins and 2,000 μg/kg for fumonisins. Clinical presentation and high levels of aflatoxin in food samples coupled with high levels of serum aflatoxin-albumin adducts among the cases support the causal role of aflatoxins.