Advances in Single-Shot Vaccine Development - Biodegradable microsphere-based systems may eliminate the need for booster shots. - BioPharm International


Advances in Single-Shot Vaccine Development
Biodegradable microsphere-based systems may eliminate the need for booster shots.

BioPharm International Supplements

In Vivo Study Results from a Prototype Single-Shot Hepatitis B Vaccination

To show the potential of the single-shot approach, prototypes were tested in in vivo studies. The results reveal the impact of the composition of the formulation on the immune response.

The OctoVAX microsphere technology is applied with the objective to reduce the number of injections to a single-shot vaccination that confers full protection against a specific infection for a period at least similar to the conventional regimen. For proof of concept of the single-shot vaccine approach, prototype vaccines were developed using the HBsAg antigen. Current practice for hepatitis B vaccination is either a two- or a three-injection regimen, consisting usually of a prime injection followed by two booster injections at 1–2 months and 3–12 months after the first administration. This vaccine consists of aluminum-adjuvanted HBsAg.

Based on the in vitro release profiles, prototype microsphere formulations were selected for further investigation of the concept. Proof of concept studies were performed by immunizing Balb/c mice with prototype microsphere vaccine formulations that combine a prime dose with a single microsphere component. This microsphere component represents the booster dose with a delayed antigen release around day 30. In these studies, the prototype single-shot vaccines were compared with two injections at day 0 and 28, representing the prime and booster dose. The potency of the vaccines to induce an antibody immune response was determined by analyzing the development, over time, of serum anti-HBsAg immunoglobulin concentration using a commercial immunoassay.

Figure 8. Antibody titers induced by prototype single-shot HBsAg vaccines based on microspheres of formulation A or B, which differ in their physical characteristics. Microspheres were either administered by themselves or mixed with aluminum hydroxide (AlOH)-adjuvanted HBsAg. Control mice received two injections of AlOH-adjuvanted HBsAg. Antibody titers are represented as geometric mean titers per group of 10 animals in relation to an international reference standard at 28, 56, and 84 days after injection.
The results of these animal studies show that the single-shot HBsAg vaccines based on the OctoVAX controlled release technology induce responses that are similar to those induced by the representative two-injection control vaccination by subcutaneous administration. Figure 8 shows that vaccines with differences in physical aspects and adjuvant presence induce antibody responses with different kinetics. Formulation A induced the desired levels of antibodies without a prime component, in contrast to formulation B, which needed an adjuvanted prime. However, even with formulation B, the data show that OctoVAX microspheres can provide a booster dose on initiation of an immune response by a prime component, providing proof of concept for the single-shot controlled delivery principle. In additional experiments, it has been shown that intramuscular application results in similar or better immune responses, which may ultimately be the preferential choice for route of administration (data not yet published).

In addition to the efficacy data, animal studies have revealed that OctoVAX microspheres are well-tolerated and induce no systemic toxicity effects.9 Furthermore, local reactogenicity was limited to minor foreign body reactions, as to be expected for any biodegradable implanted material. Therefore, it can be concluded that OctoVAX microspheres are well-tolerated and safe controlled-release vehicles that can be applied for the development of single-shot vaccines.


The development of a single-shot vaccine technology could contribute to a significant increase in vaccination coverage worldwide by improving patient compliance and lowering administration costs. To achieve this innovation, single-shot vaccines must be rationally designed. To facilitate this, complex factors in the development and manufacturing process that have a significant influence on the efficacy of the immune response must be controlled precisely during the development and manufacturing phases.

The concept of single-shot vaccination is applicable to various types of antigens and vaccines. Further research is required to investigate the influence of adjuvants and release characteristics in various vaccination regimens.

Bas Kremer, PhD, is a scientist in vaccine development, Rianne Roukema is a manager of corporate communications, and Leo de Leede is a director of preclinical research and development, all at OctoPlus NV, Leiden, the Netherlands, +31.71.5241071,


1. Van de Weert M, Hennink WE, Jiskoot W. Protein Instability in Poly(Lactic-co-Glycolic Acid) Microparticles. Pharm Res. 2000;17(10):1159–67.

2. Van Dijk-Wolthuis WN, Tsang SK, Kettenes-van den Bosch JJ, Hennink WE. A new class of polymerizable dextrans with hydrolyzable groups: Hydroxyethyl methacrylated dextran with and without oligolactate spacer. Polymer. 1997;38(25):6235–42.

3. Vlugt-Wensink KD, de Vrueh R, Gresnigt MG, Hoogerbrugge CM, van Buul-Offers SC, et al. Preclinical and clinical in vitro in vivo correlation of an hGH dextran microsphere formulation. Pharm Res. 2007;24(12):2239–48.

4. Stenekes RJ, Franssen O, van Bommel EM, Crommelin DJ, Hennink WE. The preparation of dextran microspheres in an all-aqueous system: effect of the formulation parameters on particle characteristics. Pharm Res. 1998;15(4):557–61.

5. Vlugt-Wensink KD, Meijer YJ, Steenbergen MJ, Verrijk R, Jiskoot W, et al. Effect of excipients on the encapsulation efficiency and release of human growth hormone from dextran microspheres. Eur J Pharm Biopharm. 2007;67(3):589–96.

6. Chung JT, Vlugt-Wensink KD, Hennink WE, Zhang Z. Effect of polymerization conditions on the network properties of dex-HEMA microspheres and macro-hydrogels. Int J Pharm. 2005;288(1):51–61.

7. Franssen O, Hennink WE. The preparation of dextran microspheres in an all-aqueous system: effect of the formulation parameters on particle characteristics. Pharm Res. 1998;15(4):557–61.

8. Stenekes RJ, Loebis AE, Fernandes SM, Crommelin DJ, Hennink WE. Controlled release of liposomes from biodegradable dextran microspheres: a novel delivery concept. Pharm Res. 2000;17(6):690–5.

9. Cadée JA, Brouwer LA, den Otter W, Hennink WE, van Luijn MJ. A comparative biocompatibility study of microspheres based on crosslinked dextran or poly(lactic-co-glycolic)acid after subcutaneous injection in rats. J Biomed Mater Res. 2001 Sept 15;56(4):600–9.

blog comments powered by Disqus



GPhA Issues Statement on Generic Drug Costs
November 20, 2014
Amgen Opens Single-Use Manufacturing Plant in Singapore
November 20, 2014
Manufacturing Issues Crucial to Combating Ebola
November 20, 2014
FDA Requests Comments on Generic Drug Submission Criteria
November 20, 2014
USP Joins Chinese Pharmacopoeia Commission for Annual Science Meeting
November 20, 2014
Author Guidelines
Source: BioPharm International Supplements,
Click here