Hong Kong Med J 2024 Aug;30(4):264–7 | Epub 8 Jul 2024
© Hong Kong Academy of Medicine. CC BY-NC-ND 4.0
EDITORIAL
Maternal vaccination: a promising preventive strategy to protect infants from respiratory syncytial virus
Mike YW Kwan, MSc, MRCPCH1,2; Patrick CY Chong, MRCPCH, FHKAM (Paediatrics)3; Gilbert T Chua, MB, BS, MRCPCH2,4; Marco HK Ho, MD, FRCPCH5; Liona C Poon, MD, FRCOG6
1 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong SAR, China
2 Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
3 Virtus Medical Group, Hong Kong SAR, China
4 Allergy Centre, Union Hospital, Hong Kong SAR, China
5 Lee Tak Hong Allergy Centre, Hong Kong Sanatorium & Hospital, Hong Kong SAR, China
6 Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Hong Kong SAR, China
Corresponding author: Dr Mike YW Kwan (kwanyw1@ha.org.hk)
Respiratory syncytial virus (RSV) is the leading
cause of acute lower respiratory tract infection
(ALRTI) in early childhood.1 2 In most patients, RSV
infection is self-limiting and manifests as an upper
respiratory illness.1 However, in high-risk infants
and young children, RSV infection can manifest as
bronchiolitis, pneumonia, and acute respiratory
failure; it may require hospitalisation or mechanical
ventilation and potentially result in death.1 Risk
factors for severe illness in early childhood include
prematurity, young age, and underlying conditions
(ie, congenital heart disease, chronic lung disease,
and neurodevelopmental conditions).1 3
Respiratory syncytial virus circulates year-round
globally but peaks during the winter months
in temperate regions and the rainy season in tropical
climates.4 In Hong Kong, RSV activity peaks from
March to August, when relative humidity is elevated
and wind speed is low.5 6 An understanding of
RSV seasonality facilitates effective public health
planning and resource allocation.
Whereas the implementation of infection
control measures during the coronavirus disease
2019 (COVID-19) pandemic effectively flattened the
infection curve, the subsequent relaxation of such
measures had severe impacts on RSV epidemiology
and its seasonal patterns.7 Studies in multiple
countries revealed an off-season RSV epidemic among
children aged <5 years after the peak of the COVID-19 pandemic,8 9 10 indicating a major shift in seasonality
and the need for continuous RSV surveillance.
Although RSV is a well-recognised threat
in early childhood,2 local data concerning RSV
epidemiology and disease burden remain scarce due
to the lack of systematic collection methods.5 6 The
under-recognition of RSV as a substantial contributor
to morbidity and mortality among children might
also explain the scarcity of local prevalence data. In Hong Kong, RSV currently is not considered a
notifiable communicable disease. Most patients with
clinical features of acute respiratory infection are
offered laboratory testing, particularly in clinics with
access to point-of-care testing facilities. Because
respiratory viruses cause nonspecific symptoms,
laboratory testing to identify the infectious agent is
essential for guided management strategies.1 11 Both
rapid antigen diagnostic tests and nucleic acid assays
are common laboratory tests for RSV detection,
although nucleic acid assays have higher diagnostic
accuracy than rapid antigen diagnostic tests.12
The development of multiplex nucleic acid assays
and rapid antigen diagnostic tests has allowed for
the simultaneous detection of various respiratory
pathogens13; however, the lack of access to subsidised
diagnostic tests often limits their clinical utility.
In the absence of sufficient local prevalence
data, it is important to prioritise the implementation
of territory-wide RSV surveillance and promote the
use of laboratory testing for patients with suspected
acute respiratory infection. Surveillance data can
help understand local RSV epidemiology and disease
burden (particularly among infants aged ≤6 months);
it can also inform local vaccination policy.
Globally, there were approximately 33.0 million
cases of RSV-related ALRTI among children aged
<5 years in 2019, including 3.6 million
hospitalisations.2 Notably, there were 101 400 RSV-attributable
deaths; of these, 97% occurred in low- and
middle-income countries, and 45% occurred in
children aged <6 months.2 In 1999, the estimated
annual incidence of RSV-related hospitalisation in
Hong Kong was 2.5 cases per 1000 children aged
<5 years, with a mortality rate of 0.15% among
hospitalised children.5
The economic burden of RSV infection is
substantial. The estimated global medical cost of RSV infection in young children was EUR€4.82 billion
in 2017; hospitalisation costs constituted 55% of
the global RSV economic burden, and high-income
countries carried 35% of the burden.14 In Hong
Kong, the estimated annual healthcare expenditure
for RSV-related ALRTI was HK$6.67 million.5
Multiple studies have shown that severe RSV
infection in early childhood is associated with long-term
respiratory sequelae (ie, decreased pulmonary
function,15 wheezing,16 17 and the development of
atopic asthma and clinical allergy18 19), emphasising
the high actual disease burden.
Given the absence of specific treatment for RSV
infection, the current approach to managing RSV
infection focuses on supportive care.1 11 Moreover,
although monoclonal antibody remains a promising
approach for RSV prevention in high-risk paediatric
patients,20 a safe and effective RSV vaccine remains
necessary. Considering the naïve immune system
and challenges associated with neonatal vaccination,
active immunisation of pregnant women during
the third trimester is a viable approach to protect
neonates from vaccine-preventable diseases.21
Previous efforts to develop various types of
RSV vaccines have yielded no positive outcomes.22
Efforts to understand structural differences in the
fusion (F) glycoprotein between its pre-F and pro-F
conformations have led to the development of an
effective RSV vaccine.22 The RSV pre-F protein
(RSVpreF) is the target for vaccine development
because it is an immunologically important antigen
with high conservation across all known RSV
subgroups.22
In August 2023, the United States Food
and Drug Administration approved the RSVpreF
bivalent vaccine as the first and only vaccine for use
in pregnant women to protect infants (birth until 6
months of age) from developing RSV-related ALRTI
and severe ALRTI. The decision was based on
results from the phase III MATISSE study (Maternal
Immunization Study for Safety and Efficacy), which
showed that the RSVpreF vaccine had efficacies of
81.8% and 69.4% in preventing medically attended
severe RSV-related ALRTI among newborns within
3 and 6 months after birth, respectively.23 No safety
signals were detected in maternal participants or
their infants up to 24 months of age.23 Moreover,
concurrent administration of RSVpreF with either
tetanus, diphtheria, and pertussis or inactivated
influenza vaccine was immunogenic and well-tolerated
by non-pregnant women and older adults,
respectively.24 25
In October 2023, the United States Centers for
Disease Control and Prevention issued an official
recommendation regarding the administration of a
single dose of RSVpreF bivalent vaccine to pregnant
women at 32 to 36 weeks of gestation for the
prevention of RSV-related ALRTI in infants.26
Similar to the maternal tetanus, diphtheria,
and pertussis vaccination programme, strong
government support for including the RSV
vaccine in the Vaccination Subsidy Scheme is
needed to encourage its uptake. Importantly, RSV
vaccination and counselling should be offered by
obstetricians during routine prenatal care visits
to reduce additional appointments, waiting, and
travelling time.27 28 29 Strong collaborations between
obstetricians and paediatricians allow for effective
dissemination of public messaging; obstetricians
can counsel expectant mothers about vaccine safety
and benefits, while paediatricians can reinforce the
messaging to the general public.
Clinicians should be equipped with evidence-based
information to effectively advocate for
maternal RSV vaccination. Public health agencies
and professional bodies should collaborate to
develop educational materials for the medical
community, such as clinical practice guidelines,
consensus recommendations, and continuing
medical education materials. Clinical guidelines
for simplified immunisation schedules, achieved
by combining the administration of two or more
vaccines, could address concerns related to vaccine
hesitancy.
Government-led public education campaigns
should address knowledge gaps concerning the
RSV disease burden in the paediatric population
to promote vaccine confidence and encourage
vaccination uptake. All campaign materials should
be developed in multiple languages, made available
in various formats, and disseminated through various
platforms to maximise the reach of vaccination
campaigns.
Additional data are needed to achieve full
support for maternal RSV vaccination. Data
regarding the duration of protection conferred by
maternal vaccination could provide insights into
herd immunity and the timing of booster vaccination
for children aged ≤2 years. Investigations of whether
maternal RSV-specific antibodies are present in the
breast milk of RSV-vaccinated mothers could raise
the possibility of postnatal RSV vaccination for cases
in which the vaccine is not administered during
pregnancy.
Author contributions
All authors contributed to the development of the manuscript.
All authors had full access to the data, contributed to the
study, approved the final version for publication, and take
responsibility for its accuracy and integrity.
Conflicts of interest
LC Poon has received speaker fees and consultancy payments
from Roche Diagnostics and Ferring Pharmaceuticals.
Additionally, she has received in-kind contributions from
Roche Diagnostics, Revvity Inc (formerly PerkinElmer Life and Analytical Sciences), Thermo Fisher Scientific, Ningbo
Aucheer Biological Technology Co Ltd, and GE HealthCare.
Other authors declare no conflicts of interest.
Funding/support
Funding for this study was provided by Pfizer Hong Kong.
Editorial and medical writing support was provided by Dr
Analyn Lizaso from Weber Shandwick Health HK, funded
by Pfizer Hong Kong. The funders had no role in study
design, data collection/analysis/interpretation or manuscript
preparation.
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