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. 2025 May 31:57:127187.
doi: 10.1016/j.vaccine.2025.127187. Epub 2025 May 14.

What is the current evidence base for measles vaccination earlier than 9 months of age?: Report from an informal technical consultation of the World Health Organization

Anshu Varma  1 , Shelly Bolotin  2 , Gaston De Serres  3 , Arnaud M Didierlaurent  4 , Kristen Earle  5 , Kurt Frey  6 , Susan Hahné  7 , Daniel Kapelus  8 , L Kendall Krause  9 , Kevin McCarthy  6 , William J Moss  10 , Walter A Orenstein  11 , Rob van Binnendijk  7 , Dorthe Maria Vittrup  12 , Merryn Voysey  13 , Tom Woudenberg  7 , Naor Bar-Zeev  1 , Anindya S Bose  1 , Joachim Hombach  1 , Mick N Mulders  1 , Laura Nic Lochlainn  1 , Kezia Suwintono  1 , Daniel R Feikin  1 , Natasha S Crowcroft  14
Affiliations

What is the current evidence base for measles vaccination earlier than 9 months of age?: Report from an informal technical consultation of the World Health Organization

Anshu Varma et al. Vaccine. .

Abstract

Measles is one of the most contagious vaccine preventable diseases, causing severe complications and deaths globally. While vaccination with a measles-containing vaccine (MCV) has prevented millions of measles deaths, recent trends, especially from low- and middle-income countries, are discouraging. Measles cases have increased since 2021 as MCV coverage has decreased; and an estimated 107,500 measles deaths, mostly in children under-five years, occurred in 2023. Thus, a renewed focus on proven and innovative strategies to control measles is needed. The World Health Organization (WHO) recommends a first MCV dose administered at 9-15 months of age (routine MCV1), however MCV1 below 9 months of age (early MCV1) may increase vaccination coverage because uptake of all vaccines tends to be higher the younger the child, and this might protect vulnerable infants earlier in life. However, due to concerns about possible reduced vaccine performance, early MCV1 is not routinely recommended by WHO. WHO hosted an informal technical consultation on December 6-7, 2023, in Geneva, Switzerland to evaluate recent evidence on early MCV1 and identify evidence gaps for policy making. The recent evidence suggests a robust humoral immune response shortly after early MCV1 at 5-8 months of age. Immune blunting of a routine second MCV dose (e.g., MCV2) after early MCV1 was not demonstrated in the presented data. However, 3-7 years after MCV1, children receiving early MCV1 had lower measles antibodies than children receiving routine MCV1, suggesting faster waning of immunity. The totality of evidence on immune blunting remains inconsistent. Meeting participants thought more data are needed before revisiting WHO's current recommendation for a potential revision. Evidence gaps include: understanding measles disease burden and severity in infants; early MCV1 effectiveness and duration; vaccine-induced cellular immunogenicity; whether measles in infants is acquired from other infants or older children or adults; and blunting of routine MCV2. Addressing evidence gaps through targeted studies and measles outbreak investigations, as well as evaluations of country-level introductions of early MCV1 are warranted. Ensuring high MCV1 and MCV2 coverage remains the priority in measles control.

Keywords: Early measles vaccination; Immune blunting; Immunogenicity; Vaccine effectiveness.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Authors and observers who attended the WHO meeting were subject to declaring potential competing interests. The following authors declared potential competing interests: Arnaud M. Didierlaurent is a previous employee of GlaxoSmithKline, data safety and monitoring member for AMC Biologicals, consultant for Sanofi, and speaker for Sanofi and Merck. He is a member of the Emergency Use Listing WHO Technical Advisory Group. His current research unit has research collaboration agreements with Moderna, Sanofi, and GSK; Dorthe Maria Vittrup receives financial compensation for academic teaching and public speaking on measles; L. Kendall Krause, Kevin McCarthy, Kristen Earle, and Kurt Frey are employed by the Bill & Melinda Gates Foundation which funded the meeting; Shelly Bolotin is employed by public sector entities with an interest in vaccine research and surveillance. She serves as the Director of the Centre for Vaccine Preventable Diseases at the University of Toronto. The center has received donations from Merck, Pfizer and Sanofi and adheres to governance processes at the University of Toronto to ensure it operates independently. As the Director, she has advocated for increasing immunization coverage and has publicly made statements about the safety and effectiveness of specific vaccines, including MCV. She has been funded by various Canadian Federal and other initiatives; Walter A. Orenstein is a consultant for Sanofi. The following authors declared no potential competing interests: Daniel Kapelus; Gaston De Serres; Merryn Voysey; Rob van Binnendijk; Susan Hahné; Tom Woudenberg; William J. Moss. The following observers declared potential competing interests: Ana Leticia Nery is employed by the Bill & Melinda Gates Foundation which funded this meeting; Anthony Scott receives research support for measles-related work from the Medical Research Council of the United Kingdom and Bill & Melinda Gates Foundation; Gerald Bright Businge receives research support for measles-related work from the Bill & Melinda Gates Foundation. The following observers declared no potential competing interests: Lien Anh Ha Do; Joy Lee; Katrina Kretsinger.

Figures

Fig. 1
Fig. 1
Reported measles case distribution by month and WHO region from 2018 to 2023. Abbreviation: AFR = African region; AMR = Americas region; EMR = Eastern Mediterranean region; EUR = European region; SEAR = Southeast Asian region; WHO=World Health Organization; WPR = Western Pacific region. (WHO measles reported cases and incidence).
Fig. 2
Fig. 2
Distribution of measles cases by age-group from 2012 to 2023 based on national measles case-based surveillance data retrieved from WHO regions. The analysis included laboratory confirmed, epidemiologically linked, and clinically compatible cases. Abbreviation: WHO=World Health Organization. (WHO measles surveillance data).
Fig. 3
Fig. 3
Measles antibodies in children at birth and until 12 months of age. Dashed line is the level established as the serologic correlate of protection from disease (above 0.12 IU/mL PRNT). Results were similar for MIA measurements. Data from a global seroprevalence study (2020-ongoing). Abbreviation: MIA = Multiplex Immunoassay; PRNT = Plaque Reduction Neutralization Test. (Manuscript in preparation).
Fig. 4
Fig. 4
Percentage in box indicates the percentage of children at 6 months of age with measles antibodies above the threshold of 0.12 IU/mL PRNT (level established as the serologic correlate of protection from disease). Results were similar for MIA measurements. Data from a global seroprevalence study (2020-ongoing). Abbreviation: MIA = Multiplex Immunoassay; PRNT = Plaque Reduction Neutralization Test. (Manuscript in preparation).
Fig. 5
Fig. 5
Measles antibodies in children with MCV at 6–8 months and 14 months of age, 9–12 months and 14 months of age, or only at 14 months of age, at four time points: (A) before MCV at 14 months of age, (B) 6 weeks or more after MCV at 14 months of age, (C) 1 year or more after MCV at 14 months of age, (D) 3 years or more after MCV at 14 months of age. Dashed line is the level established as the serologic correlate of protection from disease (above 0.12 IU/mL PRNT). *P ≤ .05, **P ≤ .01, and ****P ≤ .0001. Data from an observational cohort study in the Netherlands (2013-ongoing). Abbreviation: MMR = measles, mumps, and rubella vaccine. PRNT = Plaque Reduction Neutralization Test [21].
Fig. 6
Fig. 6
Children were vaccinated with MCV1 at 6 months of age and with MCV2 at 12 months of age. The proportion of children who were seropositive over time was measured at 13 months, 3 years and 5 years of age. The level established as the serologic correlate of protection from disease was 153 mIU/mL or above (seropositive) and < 153 mIU/mL (seronegative). Adjusted for test sensitivity differences. Data from an observational cohort study in South Africa (2005-ongoing). Abbreviation: MCV1 = first routinely administered dose with a measles-containing vaccine; MCV2 = second routinely administered dose with a measles-containing vaccine. (Manuscript in preparation).
Fig. 7
Fig. 7
Measles incidence attack rate per 100,000 children per age group during the extended measles outbreak from week 40, 2022, to week 18, 2023, in South Africa (about five years after introducing the early MCV1 schedule). Data from an observational cohort study in South Africa (2005-ongoing). Abbreviation: MCV1 = first routinely administered dose with a measles-containing vaccine. (Manuscript in preparation).
Fig. 8
Fig. 8
Optimal age for MCV1 in absence of MCV2 based on relation between estimated monthly measles mortality burden and MCV1 coverage. Modelling analysis using the results in [13] with modelling software in [39]. Abbreviation: MCV1 = first routinely administered dose with a measles-containing vaccine; MCV2 = second routinely administered dose with a measles-containing vaccine.
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