Neuraminidase and resistance to vaccination with live influenza A2 Hong Kong vaccines

Abstract

Thirty-seven volunteers were inoculated intranasally with living attenuated influenza A2 viruses. Rising titres of circulating antineuraminidase (AN) were detected in 14 of 17 infected volunteers. AN was also found in nasal secretions. Statistical analysis showed that there was a correlation between the titres of haemagglutination-inhibiting antibody (HI) and AN in nasal washings, and between AN in blood and washings. Resistance to infection could be predicted from antibody titres in 29 of 37 volunteers and blood AN alone predicted the outcome of 25 volunteers.

Antibody responses and resistance to challenge in volunteers vaccinated with live attenuated, detergent split and oil adjuvant A2/Hong Kong/68 (H3N2) influenza vaccines A report to the Medical Research Council Committee on Influenza and other Respiratory Virus Vaccines

“…The rises in titre of circulating AN after live and killed vaccines confirm those reported in previous studies (Slepushkin et al 1971;Schild & Newman, 1969;Downie, 1970;Kasel et al 1969). We were surprised to find such small increases in nasal N antibody titre even when good protection was produced, though our earlier studies had shown that circulating antibodies were more important than local in resistance to infection; this and the results of the statistical analysis make it clear that we cannot at the moment predict satisfactorily from antibody measurements the resistance to infection induced by vaccines.…”

“…To examine the evidence provided by the results of the serum titrations after vaccination and the outcome of the challenge, linear discriminant analysis was used, as in a previous study (Slepushkin et al 1971).…”

“…Most studies have measured circulating haemagglutination inhibiting (HI) antibody. However, it is known that vaccination produces also antineuraminidase (AN) antibody, and that both types of antibody appear in nasal secretion and serum and may be important in mediating resistance to infection (Slepushkin et al 1971). Some workers emphasize the importance of neutralizing antibody.…”

The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses

“…The apparent lack of correlation between HI and NI antibodies in the sera of one of the present groups is of interest, and the evidence suggests that the former is more closely correlated with infection than the latter. It is possible that NI antibody is of less importance in protection against influenza B virus infections than against influenza A as has been suggested by Slepushkin et al (1971), but a much larger scale survey than the present study would be required to evaluate the inter-relationship of the two antibodies in protection against influenza.…”

“…It is still not clear which of these antibodies or which combination of antibodies is essential for protection against natural infective risk in man. In recent small-scale volunteer studies it has been shown that nasal antibodies against the HA antigen (Downie & Stuart-Harris, 1970) and serum antibody against the Nase antigen (Slepushkin et al 1971) may play some part in protection against experimental challenge infection with influenza viruses, whereas for the past 20 years it has been customary to regard serum antibody against the HA antigen as the essential protective agent, and in fact all commercially available influenza vaccines are designed and assessed on their ability to produce high sustained titres of haemagglutinin-inhibiting (HI) antibody.…”