• Malaria Vaccine
• Hookworm Vaccine
• Schistosome Vaccine
• Genomic tools for Malaria
• Interactive maps and epidemiology
• Immune Evasion
• Allergy and Ascariasis
• Mosquito control
• Immunocompromised
  Hosts
• Anti-malarial drug development
• Anti-parasitic drug development
• Conflict and parasites
• Parasites of Bees
• Morgellons:
  Fact or Fiction?
• Eradication of
  Chaga’s Disease
• The world’s most successful parasite
• Guinea worm eradication

ANALYSIS

Steps toward elimination: comparison of the Human Hookworm Vaccine (HHV) and the Poliovirus vaccine

Disease elimination and/or eradication relies on the use of effective diagnostic and intervention tools. The two formulations of poliovirus vaccine, inactivated poliovirus vaccine (IPV) and oral poliovirus vaccine (OPV), are examples of widely-accepted, successful interventions that have been integral to polio eradication efforts. Given its use in controlling a once common disease, we compare the polio with the hookworm vaccine as a way of evaluating the potential medical, social, and economic impacts of the HHV.

- Protection Efficacy

-HHV: The FDA-licensed dog vaccine using irradiated L3 provided 90% protection and was sufficient to prevent pathology (19). Hence, HHV should aim for at least this level of immunity. Vaccine efficacy may depend on whether or not it is given in conjunction with anti-helminthic chemotherapy. Individual phenotype may also influence vaccine efficacy; for example, “wormy people” have higher worm burdens and may require higher doses or more frequent boosters to maintain the same level of immunity as “normal” vaccine recipients.

- Polio vaccine: Because it is difficult to predict who will develop polio-related paralysis, IPV and OPV must prevent all infections. In contrast, development of anemia directly correlates with hookworm burden and blood loss, so an effective HHV only needs to decrease the number of feeding worms in the intestines. Consequently, polio vaccine must achieve higher levels of protection (95-99% of recipients immune after 3 doses) than HHV.

- Duration of Protection

- HHV: Unknown, but antibody titers in rats inoculated with Na-ASP-2 persist for at least 3 months and are boosted by additional vaccination, results suggesting that the larval antigen may provide enduring immunity. Since rats have a 2.5-3.5 year lifespan, 3 months translates to approximately 6¼ years, based on a 75-year life expectancy. Please note that this crude calculation in no way estimates the actual duration of immunity in humans; however, it does suggest that lasting immunity is not an unreasonable goal.

- Polio vaccine: IPV and OPV provide long-lasting protection. Since hookworms are complex, multicellular organisms with many epitopes, immunity derived from one or two recombinant proteins may be more transient than that generated by whole-virus IPV and OPV vaccines.

- Vaccine Schedule

- HHV: Vaccination may require multiple injections, given that preclinical trials in rats and beagles used a three dose protocol to elicit immunity. When designing a cost-effective vaccine, it is necessary to weigh price per dose against increased immunity with each additional administration. People may be unwilling or unable to pay for vaccines that require five or six separate injections; at the same time, administering too few doses may not protect everyone from disease later on. Furthermore, in poor countries or areas of civil unrest, individuals may have difficulty adhering to prolonged, multi-dose immunization schedules, so a low dose formulation would be ideal.

- Polio vaccine: For the best results, administer three to four doses of IPV or OPV. Clearly, a single dose vaccine is not obligatory for elimination and potential eradication of a disease. If HHV were to use a three dose regimen, it could still be an effective intervention tool, as demonstrated by the polio vaccine.

- Route of administration

- HHV: Currently administered via intramuscular injection, which replicates the natural route of transmission (skin penetration). HHVI is also researching needle-free injection devices that decrease the risk of transmitting blood-borne pathogens and may be administered by non-qualified personnel (13, 20). Either type of injection is appropriate because they expose the cells that would naturally come into contact with hookworm to vaccine proteins and prime these cells so that they can generate an immune response when challenged by wild-type parasite.

- Polio vaccine: IPV also requires injection. A trial using the same needle-free injection technology is currently underway in Omam (20). If successful, this campaign may provide a model for effective HHV administration without syringes and may train healthcare workers in the use of “jet-injectors.”

- Polio vaccine: Oral administration of OPV further demonstrates how route of administration can affect vaccine efficacy. OPV is the vaccine of choice in endemic regions because it mimics the natural route of infection (fecal-oral) and produces better gastrointestinal immunity than IPV (21).

- Technology

- HHV: Recombinant protein must be purified from a genetically engineered expression host such as yeast. Making this vaccine is laborious and complicated, but perhaps enhanced productivity due to decreased anemia will make up for man-hours necessary to manufacture the vaccine.

- Polio vaccine: Production of IPV and OPV is less challenging than synthesis of recombinant HHV. The need for more sophisticated technology may result in higher production costs which could impede global access.

- Cost

- HHV: Overall cost is unknown, but because the burden of disease is greatest in low-income nations where people survive on less than US $2 a day, vaccine cannot exceed US $1 per dose (13). In the long-term, increased earning potential and productivity as a result of decreased anemia may actually offset vaccine costs.

- Polio vaccine: The current price of OPV for public health programs in developing countries is 8 US cents per dose; IPV is over 5 times more expensive (22). Considering the success of polio vaccine and its use in mass immunization programs, HHV should aim for similar prices.

- Marketing, Manufacturing, and Financing

- HHV: The vaccine has limited commercial markets because many endemic regions are impoverished, so for-profit pharmaceutical and vaccine manufacturers have little interest in supporting HHV development. Because it is an “antipoverty vaccine” with orphan status in US and Europe, HHVI will contract with vaccine manufacturers and national health ministries in innovative developing countries (IDCs) such as Brazil where hookworm is prevalent (13). Funding for procurement of vaccines in low-income endemic countries may come from PAHO Revolving Fund for Vaccine Procurement, UNICEF, and GAVI.

- Polio vaccine: Unlike HHV, existence of commercial markets in developed and developing countries provides incentive for large manufacturers. UNICEF and PAHO procure vaccines for countries that cannot afford to purchase their own. If polio is eradicated, perhaps these funds could go toward the purchase of HHV.

Vaccine Delivery

Having discussed characteristics of an effective vaccine, it is now necessary to examine the challenges associated with vaccine delivery to at risk populations. Delivery is a particularly challenging endeavor since hookworm is endemic in low-income, rural areas that often lack basic infrastructure. There are several possible options for integrating hookworm vaccination into pre-existing health care systems, each with its own advantages and disadvantages.

Integrating the hookworm vaccine into the Expanded Program on Immunization (EPI), a WHO program for vaccinating infants, is one possibility. An obvious advantage of this strategy is that EPI structures are already well established and thus, the necessary health infrastructure is already in place. However, since EPI immunizes infants, the hookworm vaccine would need to provide sufficiently long-lasting immunity before such a strategy could be safely and successfully implemented. Moreover, integrating the hookworm vaccine into EPI would not protect young children and adults who are currently at risk for hookworm infection.

Delivering hookworm vaccine at antenatal clinics is a possible means of immunizing women. Since women of reproductive age are at high risk for hookworm-induced anemia, targeting prevention efforts at this demographic group is a critical step in disease control. However, integration into antenatal care, even if combined with EPI delivery, would still not give young children and adult males access to the vaccine. Since, like women, young children are at high risk for serious hookworm morbidity, it is imperative that any vaccine delivery strategy include young children.

To ensure coverage of children, vaccination could be incorporated into school-based deworming programs. Immunization would follow a dose of albendazole which kills existing worms. Since this strategy relies on established infrastructure to target a vulnerable population and combines two interventions, it may be an important first step in vaccine delivery. However, over time, it will be necessary to expand delivery systems to cover a larger population.