A Novel Class of Antibodies For The Development Of Universal Influenza Vaccines
SUMMARY
- Influenza viruses remain a global health problem, with antigenically drifting seasonal viruses and the constant risk of zoonotic influenza virus spillovers into humans.
- Antibodies against the major surface glycoprotein hemagglutinin (HA) are critical for providing protection against influenza virus infection. HA is divided into two domains: the globular head and the stalk. Most epitopes of the HA head are highly variable and rapidly mutate to circumvent host humoral immunity. In contrast, the HA stalk is relatively conserved within and across influenza subtypes.
- Antibodies against the head and the stalk both independently correlate with protection against influenza virus infection. However, most HA-binding antibodies target variable epitopes of the HA head domain, which provide limited protection against antigenically similar influenza virus strains. Vaccine formulations that preferentially induce antibodies to conserved epitopes of the HA head and stalk domains could provide broad and potent protection against a wide array of influenza viruses.
- The faculty inventor has identified a discrete membrane-proximal anchor epitope of the HA stalk domain with potential to be broadly neutralizing and could lead to design and creation of a universal influenza virus vaccine.
FIGURE
Anchor epitope targeting mAbs are broadly neutralizing amongst H1 viruses and potently protective in vivo. (A) Neutralization potency of mAbs binding the anchor or BN stalk epitope against A/California/7/2009 H1N1. (B) Neutralization potency of anchor epitope binding mAbs against H1-expressing viruses. (C-E) Mice were prophylactically administered i.p. a cocktail of mAbs (n=5 mAbs/cocktail) against the anchor epitope or BN stalk epitope, or an anthrax specific antibody. Mice were infected 2 hours later with 10 LD50 of A/Netherlands/602/2009 H1N1. (C) Experiment design. Weight loss (D) and survival (E) of mice in each treatment group. N=10 mice per treatment group and are pooled from two independent experiments. Data in A, B, and D are represented as mean ± S.D. Data in A were analyzed by unpaired non-parametric Mann-Whitney test.
ADVANTAGES
ADVANTAGES
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Broadly neutralizing antibodies target a conserved epitope near the hemagglutinin (HA) stalk domain of influenza viruses.
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Antibodies show broad neutralizing activity against various H1-expressing influenza viruses.
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Common induction by both seasonal and pandemic influenza vaccinations
APPLICATIONS
- Universal influenza vaccines
- Broad-spectrum antiviral therapies
- Diagnostics
- Seasonal flu enhancement