Safety and Immunogenicity of DNA and MVA HIV-1 Subtype C Vaccine Prime-Boost Regimens: A Phase I Randomised Trial in HIV-Uninfected Indian Volunteers

STUDY DESIGN: A randomized, double-blind, placebo controlled phase I trial. METHODS: The trial was conducted in 32 HIV-uninfected healthy volunteers to assess the safety and immunogenicity of prime-boost vaccination regimens with either 2 doses of ADVAX, a DNA vaccine containing Chinese HIV-1 subtype C env gp160, gag, pol and nef/tat genes, as a prime and 2 doses of TBC-M4, a recombinant MVA encoding Indian HIV-1 subtype C env gp160, gag, RT, rev, tat, and nef genes, as a boost in Group A or 3 doses of TBC-M4 alone in Group B participants. Out of 16 participants in each group, 12 received vaccine candidates and 4 received placebos. RESULTS: Both vaccine regimens were found to be generally safe and well tolerated. The breadth of anti-HIV binding antibodies and the titres of anti-HIV neutralizing antibodies were significantly higher (p<0.05) in Group B volunteers at 14 days post last vaccination. Neutralizing antibodies were detected mainly against Tier-1 subtype B and C viruses. HIV-specific IFN-γ ELISPOT responses were directed mostly to Env and Gag proteins. Although the IFN-γ ELISPOT responses were infrequent after ADVAX vaccinations, the response rate was significantly higher in group A after 1(st) and 2(nd) MVA doses as compared to the responses in group B volunteers. However, the priming effect was short lasting leading to no difference in the frequency, breadth and magnitude of IFN-γELISPOT responses between the groups at 3, 6 and 9 months post-last vaccination. CONCLUSIONS: Although DNA priming resulted in enhancement of immune responses after 1(st) MVA boosting, the overall DNA prime MVA boost was not found to be immunologically superior to homologous MVA boosting. TRIAL REGISTRATION: Clinical Trial Registry CTRI/2009/091/00005

Knowledge and skills of ayurvedic and homeopathic practitioners to provide skilled birth attendance in India: An observational study

Background: To overcome the dearth of trained skilled birth attendants, mainstreaming of doctors from the alternative systems of medicine has been adopted by some states in India. Objectives: The objectives of the study were to explore the adequacy of knowledge and clinical skills of AYUSH practitioners (APs) (ayurvedic and homeopathic) engaged by the state governments to provide maternity care services, with a view to identify gaps if any, and to suggest measures for improvement. Materials and Methods: A cross-sectional observational study was conducted in three states of India (Maharashtra, Rajasthan, and Odisha). The APs were assessed for (a) knowledge of essential obstetric care and identification and management of complications of pregnancy and (b) clinical skills during provision of antenatal and postnatal care (PNC) and during the conduct of deliveries. Adequate knowledge or skill demonstration was defined as a score of 70% or more. Results: A total of 109 APs engaged in 37 peripheral level facilities were assessed. Nearly 76% of APs had adequate theoretical knowledge of essential obstetric care and identification and management of complications of pregnancy. Most APs demonstrated adequate skills while providing antenatal care but were deficient in taking past history and counseling pregnant women for danger signs during pregnancy and childbirth. APs in Maharashtra and Rajasthan had adequate skills for conducting vaginal deliveries but performed poorly in Odisha. Skills for resuscitation of newborn were deficient. Skills for providing PNC were adequate only among APs in Maharashtra. Conclusion: Through provision of appropriate in-service training and an enabling environment, APs may be a useful human resource for providing maternity care in the primary health-care settings in India

Spectrum of HIV-specific antibodies as determined by Western blot among Groups A and B vaccine recipients.

<p>Antigens recognized by HIV-specific antibodies as determined by HIV Western blot assay by group and visit after the last vaccination. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055831#pone-0055831-g002" target="_blank">Figure 2a</a> shows the frequency of volunteers recognizing each HIV antigen (Env: gp160, gp120 and gp41, Pol: p65, Gag: p55, p24 and p40) by the presence of bands in Western blot. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0055831#pone-0055831-g002" target="_blank">Figure 2b</a> shows the distribution of the spectrum of HIV-specific antibodies (number of HIV antigens identified) by Western blot. median, inter-quartile and minimum-maximum ranges are presented in the Box-Whiskers plots.</p

Flow chart of screened and enrolled volunteers.

<p>Flow chart of screened and enrolled volunteers.</p

Frequency of grade 1, 2 and 3 unsolicited adverse events recorded within 28 days post-vaccinations.

<p>Bars represent the maximum severity per volunteers within 28 days after either 2 vaccinations in Group A (separately for ADVAX and TBC-M4) or 3 vaccinations in Group B. Relative frequency of adverse events is plotted on the Y axis and Groups A, B vaccine or placebo recipients are plotted on the X-axis.</p

HIV binding ELISA antibody response rates.

<p>HIV binding ELISA antibody response rates.</p

T-cell immune responses as assessed by IFN-γ secretory ELISPOT assays against ADVAX matched peptides after 1^st and 2^nd DNA vaccinations in group A and TBC-M4 matched peptides at the other time points in group A and at all the time points in group B participants are shown.

<p>Average magnitude of IFN-γ ELISPOT responses in SFC/10⁶ cells (Y-axis) at each time point, by Groups A and B volunteers (X-axis) against different antigens are represented by different colours. 7d and 14d indicate 7 and 14 days after every vaccination, respectively. Values above the bars represent the percent of volunteers with positive responses to any or at least one peptide at that visit. The black lines and the corresponding p values showed comparison between the responses in group A and group B at days 7 and 14 after the first and second MVA vaccinations.</p