The world is facing a dire shortage of vaccines against cholera, a vaccine-preventable infectious disease associated with poverty and displacement. With climate change spurring extreme weather events such as hurricanes, flooding, and droughts, forcing migration and obstructing access to safe water and sanitation, outbreaks of cholera and other waterborne diseases have been on an alarming rise around the world.

Once detected, cholera is easily treatable with proper hydration and antibiotics, but lack of access to such healthcare can turn deadly. The WHO estimates that there are up to 4 million cases of cholera every year and up to 143,000 deaths with the caveat that cholera is often underreported due to stigma and its effect on the local economy.

Prevention is key to reducing deaths and controlling outbreaks, requiring a concerted effort to eliminate the stigma; strengthen surveillance systems to accurately determine its burden; improve access to safe water, sanitation, and routine healthcare; and provide vaccines.

Oral cholera vaccine (OCV) is a safe, effective, and affordable vaccine used in preventive mass vaccination campaigns as well as emergency responses to outbreaks, as seen in the recent shipments to Syria and Malawi to halt ongoing spread. In 2013, the WHO created a global stockpile of OCV supported by Gavi, the Vaccine Alliance, and by 2015, demand for the vaccine surpassed global supply. Today, the shortage has reached a critical point with global health agencies making daunting choices and scrambling for sustainable solutions. For instance, the WHO temporarily changed the recommended dosage for OCV from two doses to a single dose to reach more countries, even if it means shortening the duration of protection.

Two vaccines currently supply the global stockpile, both developed at IVI in partnership with VaBiotech in Vietnam and technology-transferred to Shantha Biotechnics (now part of Sanofi) in India and EuBiologics in the Republic of Korea to produce vaccines for global public use: Shanchol™ and Euvichol®/ Euvichol-Plus®, respectively, all pre-qualified by the WHO.

With Sanofi’s decision to end production of Shanchol™ in 2022 resulting in end of commercial sales in 2023 coinciding with an unprecedented spike in outbreaks and adding strain to a scarce stockpile, IVI is working to increase OCV supply in three ways: 1) assisting EuBiologics in increasing their production capacity; 2) developing new vaccines such as a cholera conjugate vaccine with the possibility of improving protection for younger children; and 3) partnering with additional vaccine manufacturers to complete technology transfers of OCV.

Technology transfer enables sustainable vaccine manufacturing and capacity-building

An essential component of IVI’s mission to accelerate vaccines for global health is technology transfer, the process of sharing the necessary materials, technical know-how, and licensing to manufacture quality vaccines at scale in addition to helping meet regulatory requirements that ensure the safety and efficacy of the vaccines. Through technology transfer, particularly with Developing Countries Vaccine Manufacturers, IVI trains local vaccine manufacturing staff and helps facilities become Good Manufacturing Practice (GMP)-compliant. This was the case with EuBiologics which had no prior experience in vaccine production and will soon become the sole manufacturer of OCV.

“OCV is a proven, highly effective preventive measure against a disease that strikes the most vulnerable. Relying on one manufacturer for any vaccine, much less a vaccine that protects against deadly epidemic diseases, is a big risk. We need more manufacturers on the marketplace to expand production capacity and increase the global supply of OCV,” says Dr. Julia Lynch, Director of IVI’s Cholera Program.

To help establish another OCV manufacturer, IVI entered a new agreement with Biovac, a bio-pharmaceutical company based in South Africa, to complete a technology and licensing transfer of OCV with funding support from the Bill & Melinda Gates Foundation and Wellcome Trust. In addition to successful collaborations with Shantha and EuBiologics leading to the first two low-cost OCVs available for the global market, this agreement with Biovac is IVI’s sixth OCV technology transfer.

In addition to filling critical gaps in OCV supply, this technology transfer will establish end-to-end production of vaccines in Africa for use in Africa—a long-awaited step forward for vaccine self-reliance on the continent.

Boosting vaccine manufacturing in Africa

In Africa, less than 1% of vaccines are locally manufactured. The COVID-19 pandemic sharply exposed this disparity, further driving vaccine inequities between high- and low-income countries in the face of a shared crisis. “It became clear that increasing self-sufficiency is important if Africa is to have better control over its own public health and vaccine supply chains,” says Dr. Morena Makhoana, CEO of Biovac.

This technology transfer between IVI and Biovac marks potentially the first instance of end-to-end manufacturing of a vaccine on the African continent.  

The transfer will begin in January 2023 with production of the first clinical trial batches expected in 2024. With the aim of first registering the product in South Africa through the national regulatory authorities by 2026, the partners will seek WHO pre-qualification (PQ) shortly after. Achieving WHO PQ, the only global medicines quality assurance program, enables agencies such as UNICEF to purchase the vaccines for global public use.

“IVI’s collaboration with Biovac to complete the transfer of OCV technology will make a significant impact on our ability to protect communities at highest risk of this deadly, though vaccine-preventable, disease,” says Dr. Jerome Kim, Director General of IVI.

IVI thanks the Gates Foundation and the Wellcome Trust for funding this effort.

by Aerie Em

Last updated December 20, 2022