HONG KONG — A new influenza A vaccine has been shown to be capable of inducing protective immune responses against multiple influenza A viruses in mice.
Researchers from the School of Public Health at the University of Hong Kong (HKU) collaborated with U.S. National Cancer Institute (NCI) scientists to develop the new vaccine, which they described in the April 1, 2014, edition of the Proceedings of the National Academy of Sciences as a breakthrough for conventional seasonal flu vaccines that protect against only one or possibly a few viral subtypes.
“We have a long-term collaboration with the NCI [which] generated the vaccine strain in the U.S., while the viral animal challenges and downstream characterization of the immune responses [triggered by the vaccine] were conducted in Hong Kong,” lead researcher Leo Poon Lit-man told BioWorld Today.
Following extensive discussions between the two, the new vaccine “is the fruit generated by the extensive efforts of both parties,” said Poon, who is an associate professor in the School of Public Health at HKU’s Li Ka Shing Faculty of Medicine.
The School of Public Health at HKU is closely involved with influenza research as a member of the Centers of Excellence for Influenza Research and Surveillance program, which is funded by U.S. National Institutes of Health National Institute of Allergy and Infectious Disease.
“We receive support from this program,” Poon noted. “Of course, this work is a major project, and we have also received support from various funding organizations, such as the University Grants Committee and the Food and Health Bureau in Hong Kong, and the NCI in the U.S.,” for influenza vaccine research and development. “This [novel] vaccine can induce a broad spectrum of protective effects against influenza viruses of different subtypes, including animal influenza viruses,” such as the highly virulent avian H7N9 influenza virus that is currently circulating in eastern China, Poon said.
“In contrast, seasonal influenza vaccines are specific only for seasonal viruses circulating in humans,” he added, pointing out that it is difficult for scientists to predict which types of a virus are likely to cause the next seasonal influenza pandemic.
“An influenza pandemic caused by a novel strain of influenza A virus that was virulent and highly transmissible among humans would be of great global concern,” HKU said in a statement released to announce the PNAS publication.
“That is the reason why we should study whether there is another way to offer a broader spectrum of protection against different subtypes of viruses,” Poon said. “This vaccine provides a promising strategy for universal protection against new and emerging influenza viruses.”
The vaccine is a live recombinant vaccinia virus called Wyeth/IL-15/5Flu that expresses multiple H5N1 influenza viral proteins, while a cytokine protein known as interleukin-15 (IL-15) is used as an adjuvant to stimulate robust immune responses in recipients of the vaccine.
“A human IL-15 gene is introduced into the vaccine strain, so that human IL-15 can be expressed after the vaccination,” Poon explained. “Previous studies, both by ourselves and by others, have demonstrated that IL-15 can be used as a molecular adjuvant and that it can enhance both T- and B-cell [immune] responses.”
The vaccinia virus is particularly useful in vaccine development, as it is also the active constituent of the vaccine used successfully to eradicate smallpox. Therefore it is already licensed for human use and could be readily adapted for mass production in case of a worldwide influenza pandemic. The HKU researchers tested the vaccine in hundreds of mice that were exposed to various viral strains, including H3N2, H1N1, H7N7 and the most recent viral strain to surface among humans, H7N9.
They demonstrated that the vaccine protected 80 percent to 100 percent of mice against infection by the avian H7N9 virus, seasonal H3N2, pandemic H1N1/2009, and the highly pathogenic H7N7 influenza A viruses, whereas no mice controls that did not receive the vaccine survived.
“This vaccine has been shown to have protective effects against H1N1, H3N2, H7N7 and H7N9 influenza viruses in mice, and we have also demonstrated that this vaccine [was effective] against H5N1 viruses in the past,” Poon said.
“The viruses tested in our studies were genetically very diverse,” he notes, “so it is believed that this vaccine would have some protective effects against influenza viruses of many other different subtypes.”
In addition, the researchers demonstrated that vaccine-induced CD4+T helper cells, which play a vital role in coordinating human immune responses, were more important than CD8+ T cells in inducing immunity.
“These results reveal an important yet underappreciated role of CD4+T cells in initiating cross-reactive protection against influenza A viruses,” said the HKU statement
Asked how long might it be before the new vaccine enters human clinical trials, Poon said that at present “it might be too early to talk about using this in humans, but we are optimistic in this regard.” In the near future, “if we have enough resources, we shall move on to [testing] in other animal models, such as ferrets.”