It is time to accelerate building local vaccine adjuvant manufacturing capacity

Recent accomplishments in vaccine adjuvant development are enabling new vaccines for previously intractable diseases, increased immunity in immunocompromised populations and greater global pandemic preparedness.^1,2 To ensure that the potential benefits of vaccine adjuvant technology are widely accessible, it is essential that adjuvant molecules and formulations, as well as the know-how to manufacture and clinically evaluate them, are made available to developing country manufacturers.

Developing country vaccine manufacturers represent a vibrant and growing community that plays an increasingly central role in the development and manufacture of vaccines globally. For instance, the Serum Institute of India produces 1.2 billion vaccine doses, making it the world’s largest vaccine manufacturer. ³ Nevertheless, the development and manufacture of modern vaccine adjuvants is still carried out largely by established companies in developed countries. The transfer of vaccine adjuvant technology to developing country partners will enable greater adjuvant manufacturing capacity and pandemic preparedness, improve local regulatory efficiency since both antigen and adjuvant will be manufactured locally, and enable manufacturers to develop novel vaccines against challenging diseases with high local burden that are not a priority for companies in the developed world. Furthermore, there is the potential for increased cost-effectiveness since labor and materials may be less expensive in developing countries, ⁴ although this is not necessarily always the case. ⁵

There are already encouraging signs that successful adjuvant technology transfer can be accomplished with significant potential impacts. For instance, since 2006 the World Health Organization’s Global Action Plan (GAP) for Influenza Vaccines (financed in large part by the Biomedical Advanced Research and Development Authority from the US Department of Human and Health Services), has enabled influenza vaccine manufacturing technology transfer, including adjuvants, to multiple developing country partners.^6–9 By 2018, these efforts are anticipated to have resulted in a global manufacturing capacity increase of more than one billion influenza vaccine doses. ¹⁰

Another encouraging example involves the novel malaria vaccine candidate, PvDBPII, in combination with the GLA-SE adjuvant, an oil-in-water emulsion containing a synthetic TLR4 ligand.^11,12 PvDBPII was developed by the International Centre for Genetic Engineering and Biotechnology in New Delhi, India, and was manufactured under cGMP conditions by Syngene International Limited in Bengaluru, India. The adjuvant manufacturing technology was transferred from IDRI in Seattle, USA to Gennova Biopharmaceuticals in Pune, India. Gennova subsequently manufactured the adjuvant under cGMP conditions and assessed physicochemical compatibility of the antigen–adjuvant mixture at their newly constructed Vaccine Formulation Center. In 2016, a phase I clinical study of the adjuvanted vaccine was initiated in India. To my knowledge, this represents the first clinical evaluation of a vaccine candidate containing a complex modern adjuvant manufactured entirely in India.

In order to accelerate the momentum represented by the above successes, it will be essential for partners from developed and developing countries to prioritize adjuvant technology as a key asset for vaccine development efforts. Partners in the developed world can engage in identifying suitable technology transfer recipients and indications of mutual interest, e.g. through Developing Country Vaccine Manufacturers Network events. Technology transfer recipients can encourage future potential partners by safeguarding the assets transferred and limiting development to those indications and areas identified through license agreements, thus protecting intellectual property of the transferring partner. Both partners can leverage creative funding mechanisms, ideally including local government partners, especially since such funding may be necessary to tackle some neglected diseases that have little profit potential. Encouragingly, funding and/or training opportunities encouraging collaborations between developed and developing countries are available.^13,14

Potential challenges associated with technology transfer efforts include lack of investment in research and development capacity by local manufacturers and governments, lack of ability to recruit and retain qualified personnel, uncertainty regarding the local vaccine market potential, inability to acquire specific equipment and supplies in a timely manner, differences in regulatory requirements from local and regional agencies, and difficulties associated with local infrastructure and environmental conditions.^5,6,15 While significant, such challenges are worth addressing in order to access the potentially significant benefits of technology transfer, including cost-effectiveness, platform innovation, faster time to local markets, ability to tailor compositions and technologies to local conditions and increased local and global health security.^4,5,15,16

Adjuvants are anticipated to play a major role in the development of next-generation vaccines as well as in global pandemic preparedness. Ensuring developing country partners can access adjuvant technology, including manufacturing and clinical testing aspects, will accelerate the impact of such vaccines in the developing world.