Recent Approaches in Hantavirus Vaccine Development

Piet Maes; Jan Clement; Marc Van Ranst


Expert Rev Vaccines. 2009;8(1):67-76. 

In This Article

Inactivated Virus Vaccines

Inactivated virus vaccines were a significant contribution to the control of infectious diseases during the 20th Century and will probably remain an important feature of vaccination strategies throughout the 21st Century. Inactivated vaccines are currently widely available for poliomyelitis, influenza, rabies, hepatitis A, tick-borne encephalitis and Japanese encephalitis.[24,25,26,27,28,29] For hantaviruses, it has been shown that high titers can be obtained by inoculation of the virus intracerebrally into rodents.[30] For Hantavax™, a formalin-inactivated Korean Hantaan virus vaccine consisting of virus amplified in mouse brains, protective efficacy has been shown in mice.[31,32,33] A recommended vaccination scheme of three doses (initial vaccination with a boost after 1 and 12 months) showed seroconversion and high specific antibody titers in humans, and this with few reported side effects. Less than 50% of the sampled population, however, produced neutralizing antibodies following the booster dose after 12 months.[31,33] The absence of any serious reported adverse event, despite the use of millions of doses during the last 10 years, suggests that this formalin-inactivated vaccine is safe for use in humans. However, it is recommended that the vaccine must be reformulated to induce a longer-lasting humoral immune response and re-evaluated to confirm the protective efficacy of this vaccine. In addition, cultured cell-derived inactivated vaccines with Hantaan virus and Seoul virus were developed in China, North Korea and Korea.[34,35,36,37,38] These vaccines were able to induce a strong humoral immune response but, again, the neutralizing response was short lived.

An inactivated bivalent hantavirus vaccine was developed in China.[39] The vaccine was derived from Syrian hamster kidney cells infected with Seoul virus strain L99 and Hantaan virus strain 84 Fli. In a clinical trial with 296 volunteers, Dong et al. found a general side-effect rate of 0.5%. Seroconversion rates of neutralizing antibody of both types of viruses were above 85% after two doses. Although three doses achieved an even higher seroconversion rate, each method has a seroconversion rate of higher than 85% with no statistically significant difference. The low side-effect rate, the high neutralizing antibody titer, together with the fact that the vaccine protects against the two endemic hantaviruses in China, makes this method a promising approach for the development of an efficient hantavirus vaccine.


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