Before we start of the details of the paper, I am sure you are wondering what it means to be a replication incompetent vaccine? A replication incompetent vaccine is a vaccine that is full of virus particles but these particles have had the coding regions for the genes necessary for additional rounds of virion replication and packaging deleted. These viruses are capable of infecting their target cells and delivering their viral payload, but then fail to continue the typical lytic pathway that leads to cell lysis and death. This is rare to have for vaccines in some sense because in order to make a vaccine you need it to replicate itself and have the virion replication but to lack this when it is injected into you.
What makes this paper rare is that they do not remove any of the viral genes they alter the genetics so the replication is dependent on an UAA (unnatural amino acid). This is seen in their Figure 1 A below:
This figure demonstrates how they used plasmids to generate cell lines with premature termination codon Influenza viruses that function in transgenic cells with UAA but do not function in conventional cells. After this they went through the process of checking to make sure the vaccine has everything that is desirable in a vaccine. They found that the replication of their PTC virus did not affect the genetic stable that made it incompetent, and probably most important to any vaccine is how safe it is to use in vivo. For this aspect of the vaccine, the authors did a fantastic job and utilized three animal models. They test the PTC virus on mice, ferrets and guinea pig and found the virus not only to be effective for offering protection against influenza but also to be able to elicit a robust humoral, mucosal and T cell mediated immunity. Both of these can be seen below. The safety of the in vivo is demonstrated in Figure 3A and the robust immune response is displayed in Figure 4A:
1.Si, L. et al. "Generation Of Influenza A Viruses As Live But Replication-Incompetent Virus Vaccines". Science 354.6316 (2016): 1170-1173. Web.
2. Jang, Yo Han and Baik-Lin Seong. "Principles Underlying Rational Design Of Live Attenuated Influenza Vaccines". Clinical and Experimental Vaccine Research 1.1 (2012): 35. Web.
3. Cohen, J. "Unfilled Vials". Science 351.6268 (2015): 16-19. Web.
All Figures were taken from the paper.