Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

Abstract

Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies.

Tetanus vaccination with a dissolving microneedle patch confers protective immune responses in pregnancy

“…Effective cross-talk between innate and adaptive immune responses generates more robust, longer-lasting immune protection [20,21]. We and other investigators have previously reported that skin immunization with metal or dissolving microneedle patches (MNPs) carrying various vaccines (influenza, inactivated poliovirus (IPV), measles, tetanus, HPV, rotavirus, BCG, malaria and RSV) confers immune responses at least non-inferior to conventional immunization as shown by lethal challenge studies, longevity of immune responses and breadth of immunity in a number of small-animal models [21][22][23][24][25][26][27][28][29][30].…”

The success of microneedle-mediated vaccine delivery into skin

“…The applied vaccine can exert a local effect in the skin and a systemic effect following uptake. 1 51,52 in mice. Microenhancer array devices were developed to cause mild abrasion of the SC.…”

Induction of broad immunity by thermostabilised vaccines incorporated in dissolvable microneedles using novel fabrication methods

“…On the day of immunization a 1cm 2 patch was applied to each ear of female 6-8 week old BALB/c mice and pressed, by hand, using a force of approximately 10-20 N per patch, in a vertical direction [15,19,20]. Patches were macroscopically inspected after removal from the ear and no material was found on them; this provided qualitative assurance that microneedles had dissolved from the adhesive backing.…”

“…Serum antigen-specific IgG responses were assessed as previously described [20] was added for one hour. Plates were washed and incubated with 50µl of TMB for thirty minutes.…”

“…Substantial research demonstrates that antibody responses to the conserved stalk region of HA provide broadly cross-reactive neutralizing antibodies (NAb) [58][59][60]. inflammatory responses at the site of immunization or in draining lymph nodes [19,20]. We hypothesize that an increase in B cell diversity that are induced by vaccine-loaded DMN patches relates to differences in the cytokine environment that may be induced using DMN patches compared to IM vaccine administration.…”