A measles and rubella vaccine microneedle patch in The Gambia: a phase 1/2, double-blind, double-dummy, randomised, active-controlled, age de-escalation trial

Read article Submitted by: Submitted by: Maria Lean, Prince of Wales Hospital, VACSIGRobert Duguid, Royal Darwin Hospital, VACSIG. Supervising consultant: Archana KoiralaBackground: Novel vaccination delivery systems are being developed to address issues with conventional needle-based vaccines, such as the need for trained personnel, reliance on cold chain storage, and the invasive nature of needle administration.Microneedle patch (MNP) vaccines represent a promising solution to these issues, making them a potential tool for mass immunisation, especially in low-income countries. MNP vaccines are easy to use, can be self-administered, and are painless, which may increase vaccination acceptance among parents and needle-averse children. MNP vaccines mechanism takes advantage of the presence of the dense network of antigen-presenting cells in the dermis, allowing for the immune response to occur without the need for antigen delivery to the subcutaneous fat or muscle.This study is the first to compare the effectiveness of MNP vaccines to the traditional needle-based subcutaneous vaccines for measles and rubella in children.Methods: This single-centre, phase 1/2, double-blind, double-dummy, randomised trial was conducted initially on healthy 18-40 years old adults (N=45), followed by healthy 15-18 months old toddlers (N=120) and healthy 9-10 months old infants (N=120), as part of an age de-escalation strategy. A head-to-head comparison was performed between the measles and rubella vaccine delivered via MNP (MRV)-MNP and the traditional subcutaneous method in infants. The primary outcome was the serum neutralising antibody concentration for measles and rubella at days 42 and 180. Results showed that in infants, seroconversion in the MNP group was comparable to the subcutaneous vaccine group: 93% vs. 90% achieved seroconversion for measles, and 100% vs. 100% for rubella following MRV-MNP and MRV-SC. Both vaccines were well-tolerated, with localised induration at the MNP site being the most common side effect.Take home message: This well-designed 1/2 phase study has generated enthusiasm for MNP vaccines as a potentially convenient and patient-friendly vaccination delivery method.The study has limitations typical of early-phase research, including a small sample size and the inclusion of only healthy participants. It could be also argued that clinical endpoints may provide a more powerful outcome than seroconversion rates, however seropositivity is generally a reliable indicator as a correlate of protection against measles and rubella. Additionally, there are concerns about the complexity and high cost of MNP manufacturing, which could impact large-scale production. Nonetheless, this technology shows promise to address limitation of traditional vaccination methods.

Image Source

Quiz Questions

1.
1. Which of the following is false?
- A.
  A) MNPs are less thermostable than traditional vaccines
- B.
  B) MNPs could be self-administered or delivered by non-medical personnel
- C.
  C) MNPs do not require reconstitution, which could result in reduced vaccine wastage
- D.
  D) Cold chain breakage can reduce the potency of traditional measles vaccine
2.
2. Which of the following is true?
- A.
  The study included malnourished infants.
- B.
  The study included infants 6-12 months of age.
- C.
  MRV-MNP/placebo-SC group had higher rates of local solicited events.
- D.
  The study evaluated different application sites and wear times.

Quiz Outcomes

1.
Results