Opposing Effects of Prior Infection versus Prior Vaccination on Vaccine Immunogenicity against Influenza A(H3N2) Viruses

Prior vaccination can alternately enhance or attenuate influenza vaccine immunogenicity and effectiveness. Analogously, we found that vaccine immunogenicity was enhanced by prior A(H3N2) virus infection among participants of the Ha Nam Cohort, Viet Nam, but was attenuated by prior vaccination among Australian Health Care Workers (HCWs) vaccinated in the same year. Here, we combined these studies to directly compare antibody titers against 35 A(H3N2) viruses spanning 1968–2018. Participants received licensed inactivated vaccines containing A/HongKong/4801/2014 (H3N2). The analysis was limited to participants aged 18–65 Y, and compared those exposed to A(H3N2) viruses circulating since 2009 by infection (Ha Nam) or vaccination (HCWs) to a reference group who had no recent A(H3N2) infection or vaccination (Ha Nam). Antibody responses were compared by fitting titer/titer-rise landscapes across strains, and by estimating titer ratios to the reference group of 2009–2018 viruses. Pre-vaccination, titers were lowest against 2009–2014 viruses among the reference (no recent exposure) group. Post-vaccination, titers were, on average, two-fold higher among participants with prior infection and two-fold lower among participants with 3–5 prior vaccinations compared to the reference group. Titer rise was negligible among participants with 3–5 prior vaccinations, poor among participants with 1–2 prior vaccinations, and equivalent or better among those with prior infection compared to the reference group. The enhancing effect of prior infection versus the incrementally attenuating effect of prior vaccinations suggests that these exposures may alternately promote and constrain the generation of memory that can be recalled by a new vaccine strain.Annette Fox, Louise Carolan, Vivian Leung, Hoang Vu Mai Phuong, Arseniy Khvorov, Maria Auladell, Yeu-Yang Tseng, Pham Quang Thai, Ian Barr, Kanta Subbarao, Le Thi Quynh Mai, H. Rogier van Doorn, and Sheena G. Sulliva

Influenza virus infection history shapes antibody responses to influenza vaccination

Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968–2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008–2018 strains were higher among participants with recent infection (34 (29–40), 187 (154–227) and 86 (72–103)) than among participants without recent infection (19 (17–22), 91 (64–130) and 38 (30–49)). On days 14 and 280, mean titer rises against 2014–2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers.Maria Auladell, Hoang Vu Mai Phuong, Le Thi Quynh Mai, Yeu-Yang Tseng, Louise Carolan, Sam Wilks, Pham Quang Thai, David Price, Nguyen Thanh Duong, Nguyen Le Khang Hang, Le Thi Thanh, Nguyen Thi Hong Thuong, Tran Thi Kieu Huong, Nguyen Thi Ngoc Diep, Vu Thi Ngoc Bich, Arseniy Khvorov, Luca Hensen, Tran Nhu Duong, Katherine Kedzierska, Dang Duc Anh, Heiman Wertheim, Scott D. Boyd, Kim L. Good-Jacobson, Derek Smith, Ian Barr, Sheena Sullivan, H. Rogier van Doorn, and Annette Fo

Influenza virus infection history shapes antibody responses to influenza vaccination

Studies of successive vaccination suggest that immunological memory against past influenza viruses may limit responses to vaccines containing current strains. The impact of memory induced by prior infection is rarely considered and is difficult to ascertain, because infections are often subclinical. This study investigated influenza vaccination among adults from the Ha Nam cohort (Vietnam), who were purposefully selected to include 72 with and 28 without documented influenza A(H3N2) infection during the preceding 9 years (Australian New Zealand Clinical Trials Registry 12621000110886). The primary outcome was the effect of prior influenza A(H3N2) infection on hemagglutinin-inhibiting antibody responses induced by a locally available influenza vaccine administered in November 2016. Baseline and postvaccination sera were titrated against 40 influenza A(H3N2) strains spanning 1968-2018. At each time point (baseline, day 14 and day 280), geometric mean antibody titers against 2008-2018 strains were higher among participants with recent infection (34 (29-40), 187 (154-227) and 86 (72-103)) than among participants without recent infection (19 (17-22), 91 (64-130) and 38 (30-49)). On days 14 and 280, mean titer rises against 2014-2018 strains were 6.1-fold (5.0- to 7.4-fold) and 2.6-fold (2.2- to 3.1-fold) for participants with recent infection versus 4.8-fold (3.5- to 6.7-fold) and 1.9-fold (1.5- to 2.3-fold) for those without. One of 72 vaccinees with recent infection versus 4 of 28 without developed symptomatic A(H3N2) infection in the season after vaccination (P = 0.021). The range of A(H3N2) viruses recognized by vaccine-induced antibodies was associated with the prior infection strain. These results suggest that recall of immunological memory induced by prior infection enhances antibody responses to inactivated influenza vaccine and is important to attain protective antibody titers

Plans for nationwide serosurveillance network in Vietnam

10.3201/eid2601.190641Emerging Infectious Diseases261E1-E