Possible strategies to utilize newer vaccine

The Respiratory Syncytial Virus (RSV) is the main agent causing hospitalizations for lower
respiratory tract infections (LRTIs) in children, especially those related to bronchiolitis and
pneumonia. Nearly 70 % of infants are infected with RSV in their first year of life, and nearly
all children (90 %) are infected within the first two years of life, with up to 40 % of these
developing a LRTI with the initial episode.Globally, RSV causes nearly 34 million LRTI and
3.4 million hospitalizations per year in infants and children < 5 years of age, with an
estimated annual increase of 10 %.In many countries, including Italy, RSV currently
represents a public health issue.

1)Monoclonal antibodies (mAbs)

For years, chances of prevention of RSV infection were confined to palivizumab, a
humanized mAb against the RSV F protein, inhibiting RSV entry and infection. Palivizumab
is administered intramuscularly on a monthly basis during the RSV season. The main
disadvantage of palivizumab is the cost and limited duration of effect based on the half-life of
the antibody. The need for repeated monthly administration is associated with missed doses,
reducing the treatment’s overall efficacy and the cost has limited its widespread use,
especially in low-income country. The aim is to target high-risk infants (e.g., prematurity,
severe bronchopulmonary dysplasia, congenital heart disease, or severe immunodeficiency)
in order to reduce severe disease in a cost-effective manner. This results in millions of infants
remaining at risk of severe or even life-threatening disease every year.
In November 2022, the EMA approved a new long-acting, human, recombinant mAb for the
prevention of RSV infection in newborns and infants during their first RSV season
(nirsevimab, Beyfortus, AstraZeneca/Sanofi Pasteur). Nirsevimab targets the highly
conserved site Ø of the prefusion conformation of the RSV F protein and contains a triple
aminoacid substitution in the Fc domain that extends its half-life, allowing for a single dose
to cover a typical RSV season in regions with temperate climates.

2)Maternal immunization
Maternal immunization is a promising potential strategy for protecting infants during their
period of greatest vulnerability to RSV infection and severe disease. Maternal immunization
avoids the challenges of direct neonatal immune system including impaired antibody affinity
maturation and less efficient antigen presentation.
The aim of vaccination in pregnancy is to boost the maternal RSV antibody levels that will be
available in neonates through the trans placental transfer and to maintain this protective level
for 3–6 months of life.. It is expected that passive immunization continues during
breastfeeding period, protecting the infant from early and recurrent infections.
Recently (August 2023), the US FDA has approved the first RSV vaccine for use in older
adults and during the third trimester of pregnancy, especially between the 32nd and 36th
week of gestational age (Pfizer’s Abrysvo). Abrysvo is a bivalent subunit vaccine candidate
based on developing the prefusion F protein as a stable molecule in this preF formulation
administered as a single-dose regimen As stated in the prescribing information of Abrysvo, a
not statistically significant disproportionate incidence of preterm births occurred between
vaccinees and placebo recipients. For this reason, it is recommended to use the vaccine
according to the indication (32th–36th weeks), because a causality between vaccination and
preterm birth cannot be excluded based on the existing data.

3)Infant immunization
Paediatric RSV vaccine development has been complicated by the immaturity and Th2-bias
of the infant immune system, by the presence of maternal neutralizing antibodies, and by the
risk of development of enhanced respiratory disease (ERD) after infection following
immunization. Vaccines under development include protein vaccines that use stabilized pre-F
protein subunits or virus-like particles, live vaccines that include attenuated RSV strains, or
virus vectors expressing RSV proteins or mRNA vaccines. High levels of immunity induction
can be reached without invading the genome of the recipient, providing a good safety profile.
At the time of writing, the US FDA has approved two RSV vaccines for use in older adults
(GSK’s Arexvy and Pfizer’s ABRYSVO),but no vaccine is still approved in paediatric
population.

Ref :
Respiratory Syncytial Virus infection: New prevention strategies Anna Chiara Vittucci
a,*, Livia Antilici a, Andrea Dotta b, Renato Cutrera c, Alberto Villani a,d

4)Co-administration
Concomitant administration of Tetanus diphtheria and pertussis (Tdap), Influenza or COVID-
19 vaccines with RSVpreF in pregnant individuals has not yet been studied. A Phase 2
placebo controlled, randomized observer-blind study (NCT04071158) evaluated safety,
tolerability, and immunogenicity of RSVpreF when administered concomitantly with Tdap in
non-pregnant women 18-49 years of age. There is no accepted correlate of protection for
pertussis vaccination. Geometric mean antibody concentrations (GMCs) to the acellular
pertussis antigens were lower in those who received Tdap concomitantly with RSVpreF,
compared to those who received Tdap alone and did not meet prespecified non-inferiority
criterion. No safety or reactogenicity concerns were identified with coadministration of Tdap,
influenza or COVID-19 vaccines in this trial. While coadministration with Tdap would likely
increase feasibility.

Ref : chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.nitag-
resource.org/sites/default/files/2023-
12/2023.10.12_NIAC_evidence_synthesis_and_recommendations_re._R.pdf
5)Public awareness and education campaigns about RSV vaccine
WASHINGTON (AUGUST 19, 2024) — The U.S. Department of Health and Human
Services (HHS) launched a new national campaign today to inform the public about common
respiratory viruses and available vaccines. The campaign, Risk Less. Do More., aims to
increase awareness of vaccines that reduce serious illness from influenza (flu), COVID-19,
and respiratory syncytial virus (RSV) in high-risk populations and to limit the spread of these
viruses among all Americans.

“Vaccines for COVID-19, flu, and RSV have helped to save millions of lives, keep countless
people out of the hospital, and provided peace of mind for the country. As fall approaches
and people spend more time indoors, I encourage everyone to protect themselves and their
loved ones by getting vaccinated,” said HHS Secretary Xavier Becerra. “The Biden-Harris
Administration is committed to providing accessible and actionable health information for all
U.S. residents, across age, geography, and race/ethnicity. We will continue working every
day to ensure the tools are available, and I hope everyone takes this opportunity to stay
healthy.”

“Respiratory illness from flu and RSV viruses usually surge during colder weather and can
cause severe disease, hospitalization, and even death,” said HHS Assistant Secretary for
Public Affairs Jeffery A Nesbit. “The goal of the Risk Less. Do More. campaign is to increase
confidence in vaccines that play an important role in preventing severe illness from these
viruses and to provide the information that the American people need to make the decision to
get vaccinated this fall and winter.”

REF : https://www.hhs.gov/about/news/2024/08/19/hhs-launches-national-public-education-
campaign-ahead-respiratory-virus-season.html

6)strengthening healthcare infrastructure and capacity for rsv vaccine

Technological innovations seem likely to deliver several interventions to prevent RSV

morbidity and mortality in the first year of life. The Roundtable concluded that major
changes are needed in both societal attitudes and health systems if these new technologies are
to achieve their full potential.

RSV infection has a well-defined seasonality in temperate countries: the infection and the
burden of illness that results are crowded into just a few months. This results in pressure on
emergency services, wards, and paediatric hospital capacity. Ideally, a prevention tool would
protect those infants born in the season or prior to the season who are vulnerable during that
season. It may be that the programmatic challenges of identifying infants falling in any
criteria to define those most at risk, together with changing hospital procedures to
accommodate such definitions and the as-yet-unknown impact of COVID-19 could result in
all infants being offered some form of RSV prevention.
Recent advances in RSV prevention strategies hold great promise but require careful
planning: both long-acting/high affinity mAbs and maternal vaccines/maternal immunisation
are both likely to be useful instruments for the prevention of RSV infection. Both provide
passive immunisation rather than the alternative of using an active RSV vaccine given to
infants that would not protect them in the first weeks of life.

Ref : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529565/

7)Cost effectiveness analysis and resource allocation

Among the cost-effectiveness analyses, there was a wide range of estimated ICERs.
Generally, the ICERs for hypothetical MI or long-acting mAb are lower (more favourable)
than for analyses of the existing short-acting mAb product palivizumab. However, when
comparing ICERs to the threshold of 1 GDP per capita in each study setting, it is unclear
whether MI or long-acting mAbs will be broadly cost-effective. Cost-effectiveness analyses
to date rely heavily on efficacy assumptions and implementation setting; as such the available
estimates and sensitivity analyses encompass a wide range of possible conclusions about the
cost-effectiveness of RSV interventions. As more precise data on intervention efficacy and
duration of protection become available from ongoing clinical trials for new long-acting mAb
and maternal vaccine products, it would allow more accurate inputs for ICER estimation and
relative value conclusions in future CEAs.
Ref : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067246/