This prospective study of 2009 pandemic influenza A infections and illnesses in a university community detected an infection frequency of 23%, with a moderate to severe ARI frequency of 9.6%. The epidemic peaked in late September–early October 2009, but infections occurred for months thereafter. Most participants were 18–30 years of age, and yet 37% had serum antibody to the pH1N1 virus at enrollment. A similar population at the same site 6 months earlier, preceding the spread of pH1N1 in the United States, exhibited an antibody frequency of 24%, suggesting that about 13% of the population was infected with the pH1N1 virus during the interval. There had been reports of outbreaks of pH1N1 influenza during that period in the United States and in Texas. Serum antibody responses to pH1N1 virus among young adults in the same population who were given seasonal inactivated vaccine containing A/Brisbane/59/07 (H1N1) virus before the appearance of pH1N1 suggests that seasonal vaccine might contribute cross-reacting antibody and priming to pH1N1 virus. However, only 10% of the study population reported prior seasonal vaccination. Consequently, prior A/H1N1 infections in combination with some pH1N1 infections preceding enrollment and not vaccinations will have induced the high frequency of preexisting pH1N1 antibody at enrollment.
Although rapid worldwide spread suggested high transmissibility, the pH1N1 viruses failed to become dominant as the cause of ARI in our population during the period of maximal occurrence. Rhinoviruses, known to be common causes of ARI in college populations in early fall, were as prominent as pH1N1 viruses as a cause of illness, and some subjects were infected with both simultaneously [21
]. Comparison of influenza and rhinovirus illnesses indicated that presentation with fever and prominent myalgias increased the likelihood that influenza virus infection induced the illness, while prominence of rhinorrhea increased the likelihood of a rhinovirus infection. However, it was not possible to make a designation of etiology based on clinical findings only.
Resistance to 2009 H1N1 influenza infection and illness in our study conformed to the well-documented inverse correlation with increasing preexposure serum anti-HA antibody. The significance of an antigenic relationship between H1N1 viruses was shown in a similar inverse correlation with the titer of antibody to the most recently preceding seasonal A/H1N1 virus. Mean titers in our HAI tests for those >25 years of age in 1977 and those 18–40 years in spring 2009 were both 1:6; titers ≥1:40 were detected in 20% of persons in our 1977 tests and ≥1:32 in 8% in 2009 tests [23
]. Despite the relatively low antibody titers in 1977, substantial immunity to A/H1N1 illness was seen in adults. The present study also found evidence of a substantial degree of immunity despite the fact that about two-thirds of the population lacked detectable serum HAI antibody to the pH1N1 virus [9
]. Presence of heterologous immunity in the absence of detectable serum HAI antibody to the epidemic virus has been shown previously [24
]. Additional evidence of preexisting immunity to pH1N1 virus in our study was indicated by the relatively low illness-to-infection ratio, the short duration of fever, the rapid disappearance of virus in respiratory secretions, and the antibody responses to a single dose of the 2009 H1N1 vaccine. The fact that immunity to pH1N1 is conveyed by prior seasonal A/H1N1 infection has been reported for animal model infections and suggested for humans [25
Three new and distinct introductions of influenza A/H1N1 viruses that caused widespread influenza occurred in 1918, 1977, and 2009 [1
]. In each instance, the viruses displayed a high capability for transmissibility and infectivity. The new strain of influenza A/H1N1, identified in the Soviet Union in 1977 (A/USSR/77 [H1N1]), proceeded to spread worldwide, with high infection rates among susceptibles that were comparable to those for the A/H2N2 and A/H3N2 pandemics of 1957 and 1968, respectively [29
]. Since then, antigenic variants of the 1977 H1N1 virus have continued as causes of human infections and illnesses. In the spring of 2009, pH1N1 virus emerged and spread rapidly worldwide. Thus, the A/H1N1 influenza viruses that emerged in 1918, 1977, and 2009 demonstrated a high capacity for transmissibility among humans. The 1918 H1N1 viruses caused high frequencies of severe influenza, a pattern also seen for the A/H2N2 and A/H3N2 virus pandemics [28
]. However, this was not clear for the 1977 A/H1N1 viruses; although high ratios of symptomatic to asymptomatic infections were reported in some outbreaks, other reports described low illness rates among susceptible groups [9
]. In 1977, antibody prevalence, vaccine responses, and subsequent surveillance data indicated a high level of immunity among those >25 years of age despite relatively low levels of antibody; they were likely exposed to A/H1N1 viruses before the viruses disappeared in 1957 [9
]. The 2009 A/H1N1 infections caused concern for a pandemic with high frequencies of severe disease that would cause high hospitalization and death rates. This concept did not adequately consider the high level of preexisting experience with A/H1N1 viruses in human populations. Based on prior experience with A/H1N1 viruses in 1976–1977, a considerable degree of immunity was expected for pH1N1 viruses among those >55 years of age and against the swine HA among those >85 years [35
]. There was uncertainty as to which age groups would be fully susceptible to the 2009 virus, with accompanying high illness rates, because circulation of A/H1N1 viruses had occurred over the 32 years since they were reintroduced in 1977.
This study has indicated that a high level of immunity existed among adults 18 years and older despite relatively low levels of antibody. The 2009 pandemic influenza experience indicated that the full susceptibility with high illness rates among healthy persons was only in children [37
]. Overall, the human experience with influenza A/H1N1 viruses over the 93-year interval since 1918 has considerably increased our knowledge of influenza and influenza immunity.