Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates

Abstract

Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA) universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.

Early cellular innate immune responses drive Zika viral persistence and tissue tropism in pigtail macaques

“…Several ZIKV vaccine strategies have been advanced to clinical trials 57 based on the success in an NHP model 21 , 58 , and although the value of these models including the PTM reported here in predicting the outcomes in humans is pending the results of these trials, the close resemblance of NHPs to humans in anatomy, immunology, and physiology, as well as our results reported here, that demonstrate close similarities between the PTM and humans in ZIKV pathogenesis, strongly indicate that this model is highly relevant for testing the efficacy of ZIKV vaccines and therapeutics. Indeed, NHP models are considered the gold standard for pre-clinical testing of most vaccines and therapeutics for a broad range of infectious diseases including HIV 59 , 60 , influenza 61 , filoviruses, and other flaviviruses 62 , 63 . Our study also shows significant differences in the immune response to ZIKV and viral distributions and persistence between males and females that highlight the need to investigate ZIKV infection and interventions separately, in both males and females, and suggests possible mechanisms that may drive distinct pathogenesis outcomes of ZIKV infection in different sexes.…”

Vaccination into the Dermal Compartment: Techniques, Challenges, and Prospects

“…Co-administration of the chemokine CCL19 was also shown to improve tumour protection [ 154 ]. Systemic administration with synthetic oligodeoxynucleotide carrying immunostimulatory CpG motifs in combination with gene gun vaccine administration was also demonstrated to improve antitumour benefit [ 155 ].…”

A Review of DNA Vaccines Against Influenza

“…Individual plasmids encoding NP ( 37 ) and M2 ( 38 ) have each been reported to decrease viral load and enhance survival against lethal heterologous challenge viruses in BALB/c mice. Combined immunisation with matrix protein, NP, and PB1 plasmids has been reported to induce protection against heterologous challenge in mice ( 39 ), pigs ( 40 ), ferrets ( 41 ), and macaques ( 42 ). Chimeric protein antigens designed to increase the breadth of host responses can be delivered by DNA vaccines.…”