Safety and Immunogenicity of an HIV Adenoviral Vector Boost after DNA Plasmid Vaccine Prime by Route of Administration: A Randomized Clinical Trial

In the development of HIV vaccines, improving immunogenicity while maintaining safety is critical. Route of administration can be an important factor.This multicenter, open-label, randomized trial, HVTN 069, compared routes of administration on safety and immunogenicity of a DNA vaccine prime given intramuscularly at 0, 1 and 2 months and a recombinant replication-defective adenovirus type 5 (rAd5) vaccine boost given at 6 months by intramuscular (IM), intradermal (ID), or subcutaneous (SC) route. Randomization was computer-generated by a central data management center; participants and staff were not blinded to group assignment. The outcomes were vaccine reactogenicity and humoral and cellular immunogenicity. Ninety healthy, HIV-1 uninfected adults in the US and Peru, aged 18-50 were enrolled and randomized. Due to the results of the Step Study, injections with rAd5 vaccine were halted; thus 61 received the booster dose of rAd5 vaccine (IM: 20; ID:21; SC:20). After the rAd5 boost, significant differences by study arm were found in severity of headache, pain and erythema/induration. Immune responses (binding and neutralizing antibodies, IFN-γ ELISpot HIV-specific responses and CD4+ and CD8+ T-cell responses by ICS) at four weeks after the rAd5 booster were not significantly different by administration route of the rAd5 vaccine boost (Binding antibody responses: IM: 66.7%; ID: 70.0%; SC: 77.8%; neutralizing antibody responses: IM: 11.1%; ID: 0.0%; SC 16.7%; ELISpot responses: IM: 46.7%; ID: 35.3%; SC: 44.4%; CD4+ T-cell responses: IM: 29.4%; ID: 20.0%; SC: 35.3%; CD8+ T-cell responses: IM: 29.4%; ID: 16.7%; SC: 50.0%.)This study was limited by the reduced sample size. The higher frequency of local reactions after ID and SC administration and the lack of sufficient evidence to show that there were any differences in immunogenicity by route of administration do not support changing route of administration for the rAd5 boost.ClinicalTrials.gov NCT00384787

Hepatitis B virus markers, alpha-fetoprotein and survival in fulminant viral hepatitis

The serological markers of hepatitis B virus and serum alpha-fetoprotein (AFP) levels have been studied in 28 consecutive cases of fulminant hepatitis, correlating the data with survival. On admission, 20 patients were found to be positive for HBsAg and eight for anti-HBs. All anti-HBs-positive cases showed high titers of anti-HBc, and six patients were positive for specific anti-HBc-IgM. DNA polymerase activity was detected in serum of 11 HBsAg-positive (55%) and four anti-HBs-positive (50%) patients. HBeAg was detected in six (21.4%) subjects (five HBsAg-positive and one anti-HBs-positive), whereas anti-HBe was present in nine (32.1%) subjects (six HBsAg-positive and three anti-HBs-positive). AFP levels greater than 60 ng/ml were found in sera of 14 patients (50%). No significant difference was evidenced in the survival rate between HBsAg-positive and anti-HBs-positive and between HBeAg-positive and HBe Ag-negative patients. However, a statistically significant difference (P < 0.05) in the survival rate was found in patients positive and negative for DNA polymerase activity and in those with AFP levels higher and lower than 60 ng/ml (P < 0.005). Pathogenetic and prognostic significance of these findings are discussed