An article by Professor Peter Hotez in Trends in Pharmacological Sciences in September 2022 explored the demand and potential supply of vaccines against malnutrition. In his article he suggests that climate change, the consequences of the COVID-19 pandemic, and “geopolitical events in Ukraine” are influencing global food shortages. He examines the “promising new interventions” that will contribute to a reduction in the “infectious causes of malnutrition” and infections that “disproportionately” cause death among malnourished patients.  

WHO’s concerns 

The WHO suggests that malnutrition “refers to deficiencies, excesses, or imbalances in a person’s intake of energy and/or nutrients”. Within the term the WHO identifies 3 specific conditions: 

  1. Undernutrition – this includes wasting, stunting, and underweight. 
  2. Micronutrient-related malnutrition – this includes micronutrient deficiencies or excesses. 
  3. Overweight, obesity, and diet-related noncommunicable diseases – these include heart disease, stroke, diabetes, and some cancers.

WHO statistics indicate that in 2020, 149 million children under 5 were estimated to be stunted, 45 million were estimated to be wasted, and 38.9 million were overweight or obese. Furthermore, “around 45% of deaths among children under 5 years of age are linked to undernutrition”.  

“The developmental, economic, social, and medical impacts of the global burden of malnutrition are serious and lasting”. 

Increasing infection risk 

Prof. Hotez warns that in LMICs “reduced nutritional intake does not occur in isolation”. In fact, “chronic infections” accelerate “both undernutrition and micronutrient-related malnutrition”. He suggests that the “African Continent and South and Southeast Asia share some of the highest rates of both iron-deficiency and protein-energy malnutrition.” In these places, high rates of infectious diseases and illnesses, as well as malaria and other conditions, exacerbate the problem.  

Hitting a hunger high 

Prof. Hotez reflects on the warning by UN Secretary General Antonio Guterres that a global food shortage is imminent. Guterres expects up to 1.6 billion people will go hungry, with 250 million on the verge of famine. In fact, the UN World Food Programme has identified millions of people at risk of famine, with hundreds of millions projected to experience mass starvation. A “driver” of this, says Prof. Hotez, is the war in Ukraine. Ukraine is home to up to 16% of the world’s corn exports and more than 40% of the world’s sunflower oil, according to the UN Food and Agriculture Organisation. A report by the African Development Bank stated that the price of wheat in Africa had increased 45% since the start of the war. In addition to conflict in Ukraine, “high temperatures from climate change, and supply-chain interruptions due to the pandemic” have played a part, says Prof. Hotez.  

Hunger and infection go hand in hand 

Prof. Hotez emphasises the relationship between malnutrition and infection, particularly chronic infections, which he suggests “cause micronutrient deficiency, undernutrition, or in some cases both”. On the unfortunate flipside, undernutrition can “often worsen or exacerbate the clinical course of infectious diseases”. A common “classic example” that Prof. Hotez cites is human hookworm infection. This produces a micronutrient deficiency. In Africa, it “often combines with malaria and schistosomiasis”. This is especially dangerous for “women of reproductive age” and children, who are vulnerable to the “combined anaemia that results from this polyparasitism”.  

Further issues arise from “persistent or recurring diarrhoea”, which cases “even greater levels of protein-energy malnutrition and stunting”. Prof. Hotez warns that the “relationship between infection and malnutrition is bidirectional”. A safe and effective solution, therefore, is required, and quickly.  

Vaccine candidates 

Prof. Hotez explores the current candidates in development, categorised into parasitic disease and bacterial vaccines.  

  • Parasitic disease vaccines: a non-profit product development partnership between European-based HookVac Consortium and the Texas Children’s Hospital Centre for Vaccine Development, a bivalent recombinant protein human hookworm vaccine has completed Phase I clinical tests in Brazil and Africa. It progresses to Phase II trials. 3 vaccines against schistosomiasis are in development for Africa and Brazil. Each comprises a single recombinant protein found on the schistosome parasite. 2 are completing Phase I testing and the 3rd is about to enter the clinic. Mosquirix, an anti-malaria vaccine by GSK and PATH has received licensure by EMA. Another recombinant protein vaccine by the Serum Institute of India was formulated with a Matrix-M adjuvant from Novovax. Known as R21, it has shown “early promise for efficacy” in Phase II-III trials in Africa. Furthermore, a live-attenuated sporozoite PfSPZ vaccine from Sanaria has shown similar promise.  
  • Bacterial vaccines: there are several shigellosis vaccines in “various stages of development”. Among them, detoxified Shigella flexneri 2a Artificial Invasin Complex (InvaplexAR-DETOX) has been developed at the Walter Reed Army Institute of Research. Also in the running are two vaccines with support from the Gates Foundation and the Wellcome Trust. ETEC vaccines are in development as well, including an oral whole cell ETVAX vaccine and an injectable subunit CssBA vaccine combined with double-mutant heat-labile toxin from the Naval Medical Research Institute, Walter Reed, and PATH. Two vaccines against a combination Shigella and ETEC are in development. Lastly, an “expanding pipeline of vaccine candidates” against tuberculosis is in development. These use an “array of biotechnologies ranging from recombinant proteins on familiar and next-generation adjuvants, virus vectors”. Some also use genetically modified live BCG to express Mycobacterium tuberculosis antigens.  
Vaccines for everyone  

Vaccines are part, but not all, of the solution. However, Prof. Hotez identifies the significant role they can play in the fight to “avert an imminent food catastrophe”. He hopes that the urgency with which COVID-19 vaccines were developed can be replicated to prioritise these life-saving vaccines. For him, this would be “consistent” with the UN Decade of Action on Nutrition commitments from 2016.  

“Until now, vaccines and vaccine development activities have not featured prominently in food system security strengthening, but this approach offers promise.” 

Prof. Hotez recognises the “unanticipated time lags and inequality gaps” from the COVID-19 pandemic but suggests that with immediate action we could avoid “all-too-familiar yet unnecessary losses”.  

To hear more about vaccine progress against some of the diseases Prof. Hotez discusses, get your tickets to the World Vaccine Congress 2022.