|Negatively stained transmission electron micrograph of herpes simplex virions. [Source: HHMI]|
The old HSV vaccine approach focused on eliciting neutralizing antibodies against the specific envelope glycoprotein gD. This protein was promising for two reasons: (1) it mediates viral entry and cell to cell spread, and (2) it stimulates a powerful immune response from the host. However, despite many attempts, there has yet to be an effective gD-based subunit vaccine.
Jacobs and his group tried something new. Instead of focusing on gD, what would happen if they got rid of it all together? They created a gD-deleted mutant HSV-2. To make the vaccine, they grew HSV-1 gD in a cell culture and then added the HSV-2 mutant to the mix. The mutant viruses soon picked up HSV-1 gD, which enabled them to infect target cells and replicate efficiently. However, without its own gD, the newly produced mutant viruses were unable to infect other cells.
This new HSV-2 vaccine was administered intravaginally and by skin contact to mice models that were later infected with wild type HSV-2. No virus was found in the vagina or any sensory nerves, where HSV is known to go latent. This vaccine also conferred immunity against both HSV-1 and HSV-2, likely due to morphological similarities between the viruses. There were also no negative side effects in immune compromised mice.
Further investigations reveal that this new vaccine strategy elicits antibody-dependent cell cytotoxicity (ADCC) instead of neutralizing antibodies, challenging old vaccine paradigms and introducing a powerful new way to confer immunity. In fact, this technology could be a scalable strategy. The HSV-2 vector could perhaps be reengineered as a vaccine against HIV, tuberculosis and other difficult-to-vaccinate mucosal infections.