Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.

<h4>Background</h4>There are increasing reports of outbreaks of measles in countries that achieved measles elimination using two doses of measles-mumps-rubella (MMR) vaccine, particularly in health care settings. While responses to a third dose of MMR in two-dose recipients have been exa...

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Main Authors: Sumanta Saha, Melanie Millier, Ari Samaranayaka, Liza Edmonds, Emma Best, James Ussher, Andrew Anglemyer, Jennifer Lee, Michael Tatley, Felicity Cutts, Rob van Binnendijk, Peter McIntyre
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0318893
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author Sumanta Saha
Melanie Millier
Ari Samaranayaka
Liza Edmonds
Emma Best
James Ussher
Andrew Anglemyer
Jennifer Lee
Michael Tatley
Felicity Cutts
Rob van Binnendijk
Peter McIntyre
author_facet Sumanta Saha
Melanie Millier
Ari Samaranayaka
Liza Edmonds
Emma Best
James Ussher
Andrew Anglemyer
Jennifer Lee
Michael Tatley
Felicity Cutts
Rob van Binnendijk
Peter McIntyre
author_sort Sumanta Saha
collection DOAJ
description <h4>Background</h4>There are increasing reports of outbreaks of measles in countries that achieved measles elimination using two doses of measles-mumps-rubella (MMR) vaccine, particularly in health care settings. While responses to a third dose of MMR in two-dose recipients have been examined, these studies have all administered MMR by the standard (intramuscular or subcutaneous) route, and data on the duration of antibody are limited. We have developed a protocol for an open-label parallel-arm randomized-controlled trial to compare measles antibody responses and safety after intradermal and aerosol administration of MMR with intramuscular, the usual mode of administration in Aotearoa (New Zealand).<h4>Methods</h4>Eligible participants are aged ≥ 18 years who have previously received two doses of the MMR vaccine and based on levels of IgG antibody to measles or mumps below the threshold for seropositivity in commercially available screening tests are required to receive the MMR vaccine prior to entering health professional training programs at Aotearoa universities. The participants will be randomized to three routes of administration (1:1:1) to receive the MMR vaccine by the intradermal (via microneedle), intrapulmonary (via vibrating mesh nebulizer), or intramuscular routes. The primary objective is to determine the proportion of participants who attain levels of measles IgG antibody above the seroprotective threshold using a multiplex bead-based immunoassay, with those in the lowest quartile validated by plaque neutralization assay, at days 6-8, 13-15, 28-42, and at 12-18 months post-vaccination. Secondary objectives include a fold increase in the geometric mean concentration of IgG antibody from baseline, and systemic and local reactions following delivery of MMR by each method. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR; https://www.anzctr.org.au/Default.aspx; trial registration no. ACTRN12623000130662).
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spelling doaj-art-6de9e4bc52d6418480ba62294f308cf32025-08-20T02:00:51ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e031889310.1371/journal.pone.0318893Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.Sumanta SahaMelanie MillierAri SamaranayakaLiza EdmondsEmma BestJames UssherAndrew AnglemyerJennifer LeeMichael TatleyFelicity CuttsRob van BinnendijkPeter McIntyre<h4>Background</h4>There are increasing reports of outbreaks of measles in countries that achieved measles elimination using two doses of measles-mumps-rubella (MMR) vaccine, particularly in health care settings. While responses to a third dose of MMR in two-dose recipients have been examined, these studies have all administered MMR by the standard (intramuscular or subcutaneous) route, and data on the duration of antibody are limited. We have developed a protocol for an open-label parallel-arm randomized-controlled trial to compare measles antibody responses and safety after intradermal and aerosol administration of MMR with intramuscular, the usual mode of administration in Aotearoa (New Zealand).<h4>Methods</h4>Eligible participants are aged ≥ 18 years who have previously received two doses of the MMR vaccine and based on levels of IgG antibody to measles or mumps below the threshold for seropositivity in commercially available screening tests are required to receive the MMR vaccine prior to entering health professional training programs at Aotearoa universities. The participants will be randomized to three routes of administration (1:1:1) to receive the MMR vaccine by the intradermal (via microneedle), intrapulmonary (via vibrating mesh nebulizer), or intramuscular routes. The primary objective is to determine the proportion of participants who attain levels of measles IgG antibody above the seroprotective threshold using a multiplex bead-based immunoassay, with those in the lowest quartile validated by plaque neutralization assay, at days 6-8, 13-15, 28-42, and at 12-18 months post-vaccination. Secondary objectives include a fold increase in the geometric mean concentration of IgG antibody from baseline, and systemic and local reactions following delivery of MMR by each method. The trial is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR; https://www.anzctr.org.au/Default.aspx; trial registration no. ACTRN12623000130662).https://doi.org/10.1371/journal.pone.0318893
spellingShingle Sumanta Saha
Melanie Millier
Ari Samaranayaka
Liza Edmonds
Emma Best
James Ussher
Andrew Anglemyer
Jennifer Lee
Michael Tatley
Felicity Cutts
Rob van Binnendijk
Peter McIntyre
Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
PLoS ONE
title Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
title_full Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
title_fullStr Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
title_full_unstemmed Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
title_short Immunogenicity and safety of measles-mumps-rubella vaccine delivered by the aerosol, intradermal and intramuscular routes in previously vaccinated young adults: a randomized controlled trial protocol.
title_sort immunogenicity and safety of measles mumps rubella vaccine delivered by the aerosol intradermal and intramuscular routes in previously vaccinated young adults a randomized controlled trial protocol
url https://doi.org/10.1371/journal.pone.0318893
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