PedVacc 002: A phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi

Njuguna, Irene; Ambler, Gwen; Reilly, Marie; Ondondo, Beatrice; Kanyugo, Mercy; Lohman-Payne, Barbara; Gichuhi, Christine; Borthwick, Nicola; Black, Antony P.; Mehedi, Shams-Rony; Sun, Jiyu; Maleche‐Obimbo, Elizabeth; Chohan, Bhavna; John‐Stewart, Grace; Jaoko, Walter; Hanke, Tomáš

doi:10.1016/j.vaccine.2014.08.034

Cited by 14 publications

(13 citation statements)

References 47 publications

(75 reference statements)

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“…With regard to temporal associations, a total of 19 articles described the time to detection of neutropenia following vaccine administration [ 11 , 12 , 14 , 15 , 19 – 33 ]. This ranged from detection on the day of vaccine administration (day 0) in one article [ 31 ] to detection 4 weeks post vaccination in 3 articles [ 14 , 22 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

et al. 2016

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BackgroundIn the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance.MethodologyWe report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context.Principal FindingsBoth in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations.ConclusionsIt is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events.Trial registrationClinicalTrials.gov NCT02017899, NCT02034500, NCT01771367, NCT01765413, NCT02523287

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Section: Resultsmentioning

confidence: 99%

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

et al. 2016

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“…In subsequent experiments, the route comparison was limited to subcutaneous versus percutaneous routes, since the subcutaneous route is more commonly used in vaccination studies of MVA vectors. As the utility of MVA as a viral vector for the expression of heterologous antigens is expanding [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]78], we also compared the antibody responses and protection conferred by vaccination with two MVA recombinants, one expressing the HSV-2 glycoprotein D, and the other expressing the H5 hemagglutinin of influenza virus rg/A Viet Nam/1203/2004 (H5N1).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from its potential use as a smallpox vaccine in immunocompromised individuals, MVA has the capacity to accommodate heterologous DNA, and express encoded proteins, thus serving as a useful viral vector in vaccine development against different types of pathogens. Several recombinant MVA vectors expressing heterologous proteins of different human pathogens are at various phases of clinical development [20,21] Some of the MVA-vectored vaccines in clinical trials include those expressing human immunodeficiency virus antigens [22,23,24], Mycobacterium tuberculosis 85A antigen [25,26,27], malaria antigens [28,29,30], human papilloma virus antigen [31], hepatitis C antigens [32,33], respiratory syncytial virus antigens [34], influenza virus antigens [35,36,37], Epstein-Barr virus antigen [38,39] and more recently, ebola virus antigens [40]. Several other MVA-vectored vaccines have also been evaluated in preclinical studies [41,42,43].…”

Section: Introductionmentioning

confidence: 99%

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines

et al. 2016

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The robustness of immune responses to an antigen could be dictated by the route of vaccine inoculation. Traditional smallpox vaccines, essentially vaccinia virus strains, that were used in the eradication of smallpox were administered by percutaneous inoculation (skin scarification). The modified vaccinia virus Ankara is licensed as a smallpox vaccine in Europe and Canada and currently undergoing clinical development in the United States. MVA is also being investigated as a vector for the delivery of heterologous genes for prophylactic or therapeutic immunization. Since MVA is replication-deficient, MVA and MVA-vectored vaccines are often inoculated through the intramuscular, intradermal or subcutaneous routes. Vaccine inoculation via the intramuscular, intradermal or subcutaneous routes requires the use of injection needles, and an estimated 10 to 20% of the population of the United States has needle phobia. Following an observation in our laboratory that a replication-deficient recombinant vaccinia virus derived from the New York City Board of Health strain elicited protective immune responses in a mouse model upon inoculation by tail scarification, we investigated whether MVA and MVA recombinants can elicit protective responses following percutaneous administration in mouse models. Our data suggest that MVA administered by percutaneous inoculation, elicited vaccinia-specific antibody responses, and protected mice from lethal vaccinia virus challenge, at levels comparable to or better than subcutaneous or intramuscular inoculation. High titers of specific neutralizing antibodies were elicited in mice inoculated with a recombinant MVA expressing the herpes simplex type 2 glycoprotein D after scarification. Similarly, a recombinant MVA expressing the hemagglutinin of attenuated influenza virus rgA/Viet Nam/1203/2004 (H5N1) elicited protective immune responses when administered at low doses by scarification. Taken together, our data suggest that MVA and MVA-vectored vaccines inoculated by scarification can elicit protective immune responses that are comparable to subcutaneous vaccination, and may allow for antigen sparing when vaccine supply is limited.

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“…Fortunately, in several phase 1 trials, no adverse events have been observed with the current pox vector and protein HIV-1 vaccine candidates, although the number of infants assessed is small. 6,7,9,10 The vaccine candidates carry no risk of HIV-1 infection because they are either protein only or contain only a single viral gene. The potential benefit is substantial, eliminating infant HIV-1 acquisition and achieving a generation free of HIV-1 infection.…”

Section: Potential Benefits and Risks Of Infant Hiv-1 Vaccinesmentioning

confidence: 99%

Infant HIV-1 Vaccines

Fouda

Cunningham

Permar

2015

JAMA

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PedVacc 002: A phase I/II randomized clinical trial of MVA.HIVA vaccine administered to infants born to human immunodeficiency virus type 1-positive mothers in Nairobi

Cited by 14 publications

References 47 publications

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

Percutaneous Vaccination as an Effective Method of Delivery of MVA and MVA-Vectored Vaccines

Infant HIV-1 Vaccines

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