Tips from the journals of the American Society for Microbiology

December 18, 2008

Killer Peptide May Offer New Therapy Against Influenza A Virus

In a new study researchers identified what appears to be the first antibody-derived peptide that inhibits the activities of harmful microbes such as influenza A virus and HIV-1. They report their findings in the December 2008 issue of the journal Antimicrobial Agents and Chemotherapy.

Influenza A viruses continue to result in hospitalization and death, especially among infants, the elderly, and immunocompromised patients worlwide. The emergence of avian influenza A virus and its ability to transfer to humans has brought about new concerns of a pandemic outbreak. Although vaccination can be an effective strategy for preventing influenza, researchers are also placing great emphasis on the discovery and development of antiviral drugs.

A killer decapeptide (KP) represents the internal image of a yeast (Pichia anomala) killer toxin that has an antimicrobial effect against pathogenic organisms. In the study activities of a KP against influenza A virus were evaluated and results showed that KP demonstrated a significant inhibitory effect on the replication of two strains of influenza A virus. Further, mice infected with influenza virus A were inoculated with KP once a day for ten days resulting in an improved survival rate of 40% and significantly decreased viral levels in their lungs.

"Overall, KP appears to be the first anti-idiotypic antibody-derived peptide that displays inhibitory activity and that has a potential therapeutic effect against pathogenic microorganisms, HIV-1, and influenza A virus by different mechanisms of action," say the researchers.

(G. Conti, W. Magliani, S. Conti, L. Nencioni, R. Sgarbanti, A.T. Palamara, L. Polonelli. 2008. Therapeutic activity of an anti-idiotypic antibody-derived killer peptide against influenza A virus experimental infection. Antimicrobial Agents and Chemotherapy, 52. 12: 4331-4337.)

New Vaccine Protects Monkeys from Pneumonic Plague

In a new study researchers from the University of Chicago, Illinois and the Lovelace Biomedical and Environmental Research Institute, Albuquerque, New Mexico developed a vaccine incorporating the protein V10 and found that it protected macaques from lethal pneumonic plague and may have implications for use in humans. They report their findings in the December 2008 issue of the journal Infection and Immunity.

Yersinia pestis is the causative agent of pneumonic plague infections in humans. Recent wildlife studies indicate that plague is rampant among rodent populations in the southwestern United States, Southeast Asia, Eastern Europe, central and southern Africa as well as South America where humans are highly susceptible to infection. The potential for large-scale human infections as well as continuously emerging antibiotic-resistant strains of Y. pestis reinforces the need for an effective vaccine.

Currently, antiplague subunit vaccines in development for human use contain recombinant low-calcium-response V antigens (rLcrV) and recombinant F1 (rF1) antigens either in equal amounts or as a fusion protein (rF1-rLcrV). In the study the researchers immunized cynomolgus macaques with an aerosol vaccine incorporating a variant of the rLcrV protein, recombinant V10 (rV10) and challenged them with a lethal dose of pneumonic plague. Results showed that rV10 prevented infection and displayed equally protective immunity to vaccines containing rLcrV or rLcrV plus rF1. Further studies showed that some antibodies of macaques immunized with rLcrV, rV10, or rF1, either alone or in combination, conferred protection in mice challenged with bubonic plague.

"Here, we show that immunization with either purified rLerV (a protein at the tip of type III needles) or a variant of this protein, recombinant V10 (rV10) (lacking amino acid residues 271 to 300), alone or in combination with rF1, prevented pneumonic lesions and disease pathogenesis," say the researchers.

(C.A. Cornelius, L.E. Quenee, K.A. Overheim, F. Koster, T.L. Brasel, D. Elli, N.A. Ciletti, O. Schneewind. 2008. Immunization with recombinant V10 protects cynomolgus macaques from lethal pneumonic plague. Infection and Immunity, 76. 12: 5588-5597.)

Natural Immune Response to HIV Not Sufficient to Prevent Secondary Superinfection

Researchers studying the phenomenon known as HIV superinfection have determined that the immune system's initial antibody response may not be sufficient to provide protection against later infection with a different HIV virus, a finding that may have significant implications for HIV vaccine development. They report their findings in the December 2008 issue of the Journal of Virology.

HIV superinfection is a condition in which a person with established human immunodeficiency virus infection acquires a second strain of the virus. Superinfection is not the same as co-infection, where an individual becomes infected with two different viruses at the same time. Recent studies suggest that as many as 5% of HIV-patients may become superinfected, however it is unclear whether superinfection only occurs in individuals with particularly poor immune responses or whether immune responses during HIV-1 infection are in general inadequate to prevent infection.

Scientists from the Fred Hutchinson Cancer Research Center and the University of Washington, Seattle compared the levels of HIV-1-specific neutralizing antibodies (NAbs) in 6 women superinfected between 1 to 5 years after initial infection to those of 18 control subjects with similar risk factors. No significant differences in the breadth or potency of NAb responses were observed just prior to the second infection. In fact, 4 of the 6 patients had relatively broad and potent NAb responses prior to superinfection. Additional analysis of the superinfecting virus variants showed no inherent resistance to antibody neutralization.

The fact that the superinfected individuals had NAbs that could neutralize the superinfecting strains led the researchers to believe that the level of NAbs elicited during natural HIV infection may not be sufficient to block HIV infection.

"An effective HIV-1 vaccine will therefore need to elicit more robust NAb responses than found during natural infection," say the researchers. "Indeed, this is the case for some other viral vaccines, such as those for hepatitis B and human papillomavirus, which elicit equivalent or higher levels of NAbs than natural infection."

(C.A. Blish, O.C. Dogan, N.R. Derby, M. Nguyen, B. Chohan, B.A. Richardson, J. Overbaugh. 2008. Human immunodeficiency virus type 1 superinfection occurs despite relatively robust neutralizing antibody responses. Journal of Virology, 82. 24: 12094-12103.)

American Society for Microbiology

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