Cross-reactive antibody responses and their role in protection against influenza virus infection and disease

 The Krammer laboratory (along with others) has demonstrated the existence of cross-reactive and cross-neutralizing antibodies against divergent hemagglutinins (HAs) and neuraminidases (NAs) in humans.  Such responses may protect humans against potentially pandemic, zoonotic influenza viruses, and understanding how the breadth of cross-reactivity differs across animal models is essential to developing a universal influenza vaccine, which aims to boost cross-reactive, HA stalk antibodies. Importantly, non-neutralizing antibodies may also protect animals in vivo via antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and complement dependent cytotoxicity (CDC).  The lab has demonstrated this directly by studying monoclonal antibodies against H7N9.

Developing a universal influenza virus vaccine

The influenza virus mutates and escapes human immunity at a rapid rate, necessitating annual vaccine reformulation. Working closely with the laboratory of Drs. Peter Palese and Adolfo García-Sastre, the Krammer laboratory has worked to develop broader vaccines that would protect against a range of influenza virus subtypes. One approach involves vaccination with chimeric viruses to boost antibodies to the highly conserved HA stalk domain.  The structure of the viral NA is also highly conserved, making it an attractive vaccine target.  The lab has shown that vaccination with purified NA alone can protect against influenza virus infection and we have isolated murine anti-NA antibodies that inhibit a broad range of influenza viruses; such antibodies can be humanized and used therapeutically.

Developing vaccines and novel therapeutics against emerging viruses

Using our insect cell recombinant protein core and hybridoma technology, researchers at the Krammer laboratory are working to develop vaccines and antibodies against  emerging zoonotic viruses such as hantaviruses, filoviruses, arenaviruses and avian influenza viruses like H5N1, H6N1, H7N9 and H10N8.  Such viruses may propagate asymptomatically in an animal reservoir but have the potential to lethally infect humans upon close contact.