Evidence map›Paper›PMID 19605598›Full record

Trial reportClinical and vaccine immunology : CVI2009

Safety and immunogenicity of the Merck adenovirus serotype 5 (MRKAd5) and MRKAd6 human immunodeficiency virus type 1 trigene vaccines alone and in combination in healthy adults.

Clayton Harro, Xiao Sun, Jon E Stek, Randi Y Leavitt, Devan V Mehrotra, Fubao Wang, Andrew J Bett, Danilo R Casimiro, John W Shiver, Mark J DiNubile and 2 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Clinical and vaccine immunology : CVI, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00850616 (A Phase I Dose Ranging Study of the Safety, Tolerability, and Immunogenicity of a 3-Dose Regimen of the MRKAd5 HIV-1 Trigene and the MRKAd6 HIV-1 Trigene Vaccines Alone and in Combination in Healthy Adults), which is not on this map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00850616 phase1completednot on this map

A Phase I Dose Ranging Study of the Safety, Tolerability, and Immunogenicity of a 3-Dose Regimen of the MRKAd5 HIV-1 Trigene and the MRKAd6 HIV-1 Trigene Vaccines Alone and in Combination in Healthy Adults

TypeinterventionalSponsorMerck Sharp & Dohme LLCRan2005 to 2011Enrolled147ConditionsHIV, HIV InfectionsArmsV526, Comparator: Placebo to V526
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Clayton HarroCenter for Immunization Research, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD 21205, USA. charro@jhsph.edu
Xiao Sun
Jon E Stek
Randi Y Leavitt
Devan V Mehrotra
Fubao Wang
Andrew J Bett
Danilo R Casimiro
John W Shiver
Mark J DiNubile
Erin Quirk
Merck V526-001 Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Preexisting immunity to adenovirus serotype 5 (Ad5) diminishes immune responses to vaccines using Ad5 as a vector. Alternate Ad serotypes as vaccine vectors might overcome Ad5-specific neutralizing antibodies and enhance immune responses in populations with a high prevalence of Ad5 immunity. To test this hypothesis, healthy human immunodeficiency virus (HIV)-seronegative adults were enrolled in a blinded, randomized, dose-escalating, placebo-controlled study. In part A, subjects with baseline Ad6 titers of < or = 18 received the Merck Ad6 (MRKAd6) HIV type 1 (HIV-1) trigene vaccine at weeks 0, 4, and 26. In part B, subjects stratified by Ad5 titers (< or = 200 or >200) and Ad6 titers (< or = 18 or >18) received the MRKAd5-plus-MRKAd6 (MRKAd5+6) HIV-1 trigene vaccine at weeks 0, 4, and 26. Immunogenicity was assessed by an enzyme-linked immunospot (ELISPOT) assay at week 30. No serious adverse events occurred. MRKAd6 trigene vaccine recipients responded more often to Nef than to Gag or Pol. In part A, ELISPOT response rates to > or = 2 vaccine antigens were 14%, 63%, and 71% at 10(9), 10(10), and 10(11) viral genomes (vg)/dose, respectively. All responders had positive Nef-specific ELISPOT results. In part B, Nef-ELISPOT response rates at 10(10) vg/dose of the MRKAd5+6 trigene vaccine were 50% in the low-Ad5/low-Ad6 stratum (n = 8), 78% in the low-Ad5/high-Ad6 stratum (n = 9), 75% in the high-Ad5/low-Ad6 stratum (n = 8), and 44% in the high-Ad5/high-Ad6 stratum (n = 9). The MRKAd6 and MRKAd5+6 trigene vaccines elicited dose-dependent responses predominantly to Nef and were generally well tolerated, indicating that Ad6 should be considered a candidate vector for future vaccines. Although small sample sizes limit the conclusions that can be drawn from this exploratory study, combining two Ad vectors may be a useful vaccine strategy for circumventing isolated immunity to a single Ad serotype.

Indexed as

Adenoviruses, HumanAdultAIDS VaccinesAntibodies, ViralDouble-Blind MethodFemalegag Gene Products, Human Immunodeficiency VirusHIV-1HumansLeukocytes, MononuclearMaleMiddle Agednef Gene Products, Human Immunodeficiency Viruspol Gene Products, Human Immunodeficiency VirusVaccines, SyntheticYoung AdultAIDS VaccinesAntibodies, Viralgag Gene Products, Human Immunodeficiency Virusnef Gene Products, Human Immunodeficiency Virusnef protein, Human immunodeficiency virus 1pol Gene Products, Human Immunodeficiency VirusVaccines, Synthetic

Identifiers

PMID19605598
PMCPMC2745015

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.