Kinetics of Serological Responses in Critically Ill Patients Hospitalized With 2009 Pandemic Influenza A(H1N1) Virus Infection in Canada, 2009–2011

Abstract

Background The kinetics of the antibody response during severe influenza are not well documented. Methods Critically ill patients infected with 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), confirmed by reverse-transcription polymerase chain reaction analysis or seroconversion (defined as a ≥4-fold rise in titers), during 2009–2011 in Canada were prospectively studied. Antibody titers in serially collected sera were determined using hemagglutinin inhibition (HAI) and microneutralization assays. Average antibody curves were estimated using linear mixed-effects models and compared by patient outcome, age, and corticosteroid treatment. Results Of 47 patients with A(H1N1)pdm09 virus infection (median age, 47 years), 59% had baseline HAI titers of <40, and 68% had baseline neutralizing titers of <40. Antibody titers rose quickly after symptom onset, and, by day 14, 83% of patients had HAI titers of ≥40, and 80% had neutralizing titers ≥40. Baseline HAI titers were significantly higher in patients who died compared with patients who survived; however, the antibody kinetics were similar by patient outcome and corticosteroid treatment. Geometric mean titers over time in older patients were lower than those in younger patients. Conclusions Critically ill patients with influenza A(H1N1)pdm09 virus infection had strong HAI and neutralizing antibody responses during their illness. Antibody kinetics differed by age but were not associated with patient outcome.

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population

“…Although, our results support the assumption that antibody measured in these 262 specimens are representative of levels present prior to infection, this cannot be definitively determined 263 without paired pre-infection specimens. One recent study of antibody kinetics in patients hospitalized 264 found that HAI titers rose rapidly after infection with >80% having HAI titers ≥40 within two weeks [25]; 265 in our study, 89% of patients had specimens collected ≤6 days after illness onset. Similarly, vaccinated 266 subjects had higher HAI and NAI titers against all measured influenza antigens suggesting that these 267 antibodies were produced in response to influenza vaccination.…”

Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population

“…However, this result is consistent with challenge studies finding little antibody response before 7 days post-infection [25]. Another recent study of antibody kinetics in patients hospitalized found that HAI titers rose rapidly after infection with >80% having HAI titers ≥40 within two weeks [26]; in our study, 89% of patients had specimens collected ≤6 days after illness onset. Similarly, vaccinated subjects had higher HAI and NAI titers against all measured influenza antigens suggesting that these antibodies were produced in response to influenza vaccination.…”

Cell-to-Cell Spread Blocking Activity Is Extremely Limited in the Sera of Herpes Simplex Virus 1 (HSV-1)- and HSV-2-Infected Subjects

“…Overall, the presence of neutralizing antibodies is considered an important marker of protection against many viruses (23)(24)(25). However, it is also well known that the detection of only neutralizing antibodies can likewise be elusive for many viruses (26). Many anti-HSV vaccine attempts, trials, and projects, with the aim of eliciting neutralizing serum antibodies, such as those using whole virions or full-length viral immunogenic proteins, have been carried out in recent decades without much success in conferring long-lasting reduction of both clinical HSV recurrences and virus shedding rates (5)(6)(7).…”