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Study: Neuraminidase antibodies help protect against flu
Filed Under:
Influenza Vaccines
Robert Roos | News Editor | CIDRAP News
| Apr 13, 2015
A study from the University of Michigan and the Centers for Disease Control and Prevention has yielded what's being called "convincing" evidence that antibodies to the influenza virus protein neuraminidase (NA) contribute to protection against flu in people who have received a flu shot.
Neuraminidase and hemagglutinin (HA) are the surface proteins on flu viruses and the components most visible to the immune system; HA enables the virus to enter a host cell, while NA allows new viral copies to leave the cell in search of others to infect. Current flu vaccines are designed to target the HA component.
In the study, Arnold Monto, MD, and colleagues measured the levels of HA and NA antibodies in stored serum left over from a randomized trial of inactivated flu vaccine (IIV) and live attenuated flu vaccine (LAIV) and assessed the independent contribution of the antibodies to protection from the virus. They used HA inhibition (HAI), microneutralization (MN), and a "newly standardized" NA-inhibition (NAI) test to measure antibody titers.
The team used the HA and MN tests on samples from 497 participants, including 103 who had confirmed flu and 394 who did not. Because of the complexity of the MN assay, the investigators used a smaller subset of 171 samples for that test, including 81 from cases and 90 from non-cases.
The NAI assay showed vaccine-induced NA antibodies in 37% of IIV recipients, while the HAI and MN tests showed HA antibody responses in 77% and 67%, respectively. In LAIV recipients, the antibody responses were seen in 6% (NAI), 21% (HAI), and 17% (MN). In IIV recipients, as NA antibody levels rose, the likelihood of infection (vaccine failure) fell, as was also true for HA antibody levels.
The authors said their analyses "suggested an independent role for NAI antibody in protection which was similar in IIV, LAIV and placebo groups." They concluded, "While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered."
[h=3]'Most convincing evidence to date'[/h] In an accompanying editorial, Laura Eckard, and Richard Webby, PhD, of St. Jude Children's Research Hospital in Memphis commented that NA antibodies have been shown to reduce disease severity and mortality in various animal studies and that NA response may have moderated the 1968 flu pandemic, since the NA component of the pandemic H3N2 virus was left over from the previously dominant H2N2 flu strain.
"Monto and colleagues now provide the most convincing evidence to date that NA-directed humoral immunity is protective, and is a correlate of protection in its own right," Eckard and Webby wrote. They added that the key message of the study is that "as NAI titers rose, the frequency of vaccine failure fell," which suggests that "vaccines can induce NA-directed antibody responses that are independently predictive of protection."
Eckard and Webby added that it's probably premature to propose that a minimum level of NA be required in IIV, but they agree with the researchers' suggestion that NA content be considered as new flu vaccines are developed.
See also:
Apr 8 J Infect Dis study
Apr 8 J Infect Dis editorial
Study: Neuraminidase antibodies help protect against flu
Filed Under:
Influenza Vaccines
Robert Roos | News Editor | CIDRAP News
| Apr 13, 2015
A study from the University of Michigan and the Centers for Disease Control and Prevention has yielded what's being called "convincing" evidence that antibodies to the influenza virus protein neuraminidase (NA) contribute to protection against flu in people who have received a flu shot.
Neuraminidase and hemagglutinin (HA) are the surface proteins on flu viruses and the components most visible to the immune system; HA enables the virus to enter a host cell, while NA allows new viral copies to leave the cell in search of others to infect. Current flu vaccines are designed to target the HA component.
In the study, Arnold Monto, MD, and colleagues measured the levels of HA and NA antibodies in stored serum left over from a randomized trial of inactivated flu vaccine (IIV) and live attenuated flu vaccine (LAIV) and assessed the independent contribution of the antibodies to protection from the virus. They used HA inhibition (HAI), microneutralization (MN), and a "newly standardized" NA-inhibition (NAI) test to measure antibody titers.
The team used the HA and MN tests on samples from 497 participants, including 103 who had confirmed flu and 394 who did not. Because of the complexity of the MN assay, the investigators used a smaller subset of 171 samples for that test, including 81 from cases and 90 from non-cases.
The NAI assay showed vaccine-induced NA antibodies in 37% of IIV recipients, while the HAI and MN tests showed HA antibody responses in 77% and 67%, respectively. In LAIV recipients, the antibody responses were seen in 6% (NAI), 21% (HAI), and 17% (MN). In IIV recipients, as NA antibody levels rose, the likelihood of infection (vaccine failure) fell, as was also true for HA antibody levels.
The authors said their analyses "suggested an independent role for NAI antibody in protection which was similar in IIV, LAIV and placebo groups." They concluded, "While NAI antibody is not produced to a large extent in response to current IIV, it appears to have an independent role in protection. As new influenza vaccines are developed, NA content should be considered."
[h=3]'Most convincing evidence to date'[/h] In an accompanying editorial, Laura Eckard, and Richard Webby, PhD, of St. Jude Children's Research Hospital in Memphis commented that NA antibodies have been shown to reduce disease severity and mortality in various animal studies and that NA response may have moderated the 1968 flu pandemic, since the NA component of the pandemic H3N2 virus was left over from the previously dominant H2N2 flu strain.
"Monto and colleagues now provide the most convincing evidence to date that NA-directed humoral immunity is protective, and is a correlate of protection in its own right," Eckard and Webby wrote. They added that the key message of the study is that "as NAI titers rose, the frequency of vaccine failure fell," which suggests that "vaccines can induce NA-directed antibody responses that are independently predictive of protection."
Eckard and Webby added that it's probably premature to propose that a minimum level of NA be required in IIV, but they agree with the researchers' suggestion that NA content be considered as new flu vaccines are developed.
See also:
Apr 8 J Infect Dis study
Apr 8 J Infect Dis editorial