---
title: "Vaccine strategies and development during the 1968 H3N2 influenza pandemic"
id: "pubmed-42391691"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42391691"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42391691/"
doi: "10.1016/j.vaccine.2026.128877"
published_at: "2026-08-30T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Vaccine strategies and development during the 1968 H3N2 influenza pandemic
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42391691
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42391691/)
- **DOI:** [10.1016/j.vaccine.2026.128877](https://doi.org/10.1016%2Fj.vaccine.2026.128877)
- **Published At:** 2026-08-30T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The 1968 emergence of influenza A virus subtype **H3N2** caused a global pandemic (1968 H3N2pdm) with estimates of up to two million fatalities linked to the event. - The H3N2 subtype became established and continues to circulate as seasonal **influenza A virus** in humans. - Concerns about future IAV pandemics persist due to zoonotic spill-over of avian viruses such as **H5N1**, discovery of novel IAVs with pandemic potential, and antigenic change in seasonal strains. - The review summarizes proactive actions, precautionary measures and **vaccination strategies** used before, during and after the 1968 pandemic. - It outlines the emergence and global spread of the 1968 H3N2 pandemic and links that history to lessons for modern preparedness. - The authors argue for updating historical strategies with insights from the **COVID-19 pandemic** to improve readiness for future IAV pandemics. - Emphasis is placed on improving countermeasures, surveillance and public communication to limit the impact of future influenza pandemics. - Keywords highlighted by the authors include 1968 pandemic, **H3N2**, Hong Kong pandemic, Influenza, and Vaccine development. - The review is classified as a Review article in Vaccine (2026) and lists potential conflicts of interest for one author related to vaccine and assay development; full competing interests are disclosed in the source. - MeSH indexing in the source includes Influenza A Virus, H3N2 Subtype immunology, Influenza Vaccines immunology, Influenza, Human epidemiology and immunology, and related terms.
## Clinical Analysis & Structured Key Points
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Epub 2026 Jul 2. # Vaccine strategies and development before and during the 1968 H3N2 influenza pandemic [Nico Joel Halwe](https://pubmed.ncbi.nlm.nih.gov/?term=Halwe+NJ&cauthor_id=42391691)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42391691/#full-view-affiliation-1 "Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: nico.halwe@lbg.ac.at."), [Florian Krammer](https://pubmed.ncbi.nlm.nih.gov/?term=Krammer+F&cauthor_id=42391691)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42391691/#full-view-affiliation-2 "Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Vaccine Research and Pandemic Preparedness \(C-VaRPP\), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@meduniwien.ac.at.") Affiliations Expand ### Affiliations * 1 Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: nico.halwe@lbg.ac.at. * 2 Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@meduniwien.ac.at. * PMID: **42391691** * DOI: [ 10.1016/j.vaccine.2026.128877 ](https://doi.org/10.1016/j.vaccine.2026.128877) Item in Clipboard Review # Vaccine strategies and development before and during the 1968 H3N2 influenza pandemic Nico Joel Halwe et al. Vaccine. 2026. Show details Display options Display options Format Abstract PubMed PMID Vaccine Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Vaccine%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Vaccine%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42391691/) . 2026 Aug 30:89:128877. doi: 10.1016/j.vaccine.2026.128877. Epub 2026 Jul 2. ### Authors [Nico Joel Halwe](https://pubmed.ncbi.nlm.nih.gov/?term=Halwe+NJ&cauthor_id=42391691)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42391691/#short-view-affiliation-1 "Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: nico.halwe@lbg.ac.at."), [Florian Krammer](https://pubmed.ncbi.nlm.nih.gov/?term=Krammer+F&cauthor_id=42391691)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42391691/#short-view-affiliation-2 "Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Vaccine Research and Pandemic Preparedness \(C-VaRPP\), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@meduniwien.ac.at.") ### Affiliations * 1 Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria. Electronic address: nico.halwe@lbg.ac.at. * 2 Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness at the Medical University of Vienna, 1090 Vienna, Austria; Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Medical University of Vienna, 1090 Vienna, Austria; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Center for Vaccine Research and Pandemic Preparedness (C-VaRPP), Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: florian.krammer@meduniwien.ac.at. * PMID: **42391691** * DOI: [ 10.1016/j.vaccine.2026.128877 ](https://doi.org/10.1016/j.vaccine.2026.128877) Item in Clipboard Full text links Cite Display options Display options Format Abstract PubMed PMID ## Abstract Nearly 60 years ago, in 1968, the global population was confronted with the emerging pandemic influenza A virus (IAV) subtype H3N2 (1968 H3N2pdm). An estimate of up to two million fatalities have been linked to 1968 H3N2pdm, and the H3N2 subtype continues to circulate as seasonal IAV among humans until today. The last IAV pandemic dates back to the year 2009 but concerns about a new IAV pandemic in the near future are increasing. The global spread of H5N1 highly pathogenic avian influenza virus and its spill-over into new mammalian hosts, discovery of novel influenza A virus with zoonotic or even pandemic potential, as well as seasonal influenza viruses undergoing antigenic changes necessitate constant vigilance. Here, we highlight the proactive actions, precautionary measures and vaccination strategies used during the 1968 H3N2 IAV pandemic. Our review highlights the emergence and spread of 1968 H3N2pdm over the course of the pandemic, alongside a delineation of vaccine development before, during and after the 1968 pandemic. Updating these strategies in the context of new findings combined with our experiences during the coronavirus disease 2019 (COVID-19) pandemic is necessary to improve preparedness for the next pandemic. Influenza viruses with zoonotic potential will remain a constant threat to public health, and improving countermeasures and communication to the public is key to limit the pandemic ramifications. **Keywords:** 1968 pandemic; H3N2; Hong Kong pandemic; Influenza; Vaccine development. Copyright © 2026. Published by Elsevier Ltd. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Florian Krammer declares the following conflicts of interest. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines, influenza virus vaccines and influenza virus therapeutics which list FK as co-inventor and FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Castlevax, to develop SARS-CoV-2 vaccines. FK is co-founder and scientific advisory board member of Castlevax. FK has consulted for Merck, GSK, Sanofi, Gritstone, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development and with Sanofi on tracking SARS-CoV-2 variants. ## Similar articles * [ Vaccination with Recombinant Parainfluenza Virus 5 Expressing Neuraminidase Protects against Homologous and Heterologous Influenza Virus Challenge. ](https://pubmed.ncbi.nlm.nih.gov/28931689/) Mooney AJ, Gabbard JD, Li Z, Dlugolenski DA, Johnson SK, Tripp RA, He B, Tompkins SM.Mooney AJ, et al.J Virol. 2017 Nov 14;91(23):e01579-17. doi: 10.1128/JVI.01579-17. Print 2017 Dec 1.J Virol. 2017.PMID: 28931689Free PMC article. * [ Improving the selection and development of influenza vaccine viruses - Report of a WHO informal consultation on improving influenza vaccine virus selection, Hong Kong SAR, China, 18-20 November 2015. ](https://pubmed.ncbi.nlm.nih.gov/28131392/) Hampson A, Barr I, Cox N, Donis RO, Siddhivinayak H, Jernigan D, Katz J, McCauley J, Motta F, Odagiri T, Tam JS, Waddell A, Webby R, Ziegler T, Zhang W.Hampson A, et al.Vaccine. 2017 Feb 22;35(8):1104-1109. doi: 10.1016/j.vaccine.2017.01.018. Epub 2017 Jan 25.Vaccine. 2017.PMID: 28131392Free PMC article.Review. * [ Are we serologically prepared against an avian influenza pandemic and could seasonal flu vaccines help us? ](https://pubmed.ncbi.nlm.nih.gov/39745389/) Sanz-Muñoz I, Sánchez-Martínez J, Rodríguez-Crespo C, Concha-Santos CS, Hernández M, Rojo-Rello S, Domínguez-Gil M, Mostafa A, Martinez-Sobrido L, Eiros JM, Nogales A.Sanz-Muñoz I, et al.mBio. 2025 Feb 5;16(2):e0372124. doi: 10.1128/mbio.03721-24. Epub 2024 Dec 31.mBio. 2025.PMID: 39745389Free PMC article. * [ Diversifying T-cell responses: safeguarding against pandemic influenza with mosaic nucleoprotein. ](https://pubmed.ncbi.nlm.nih.gov/39898643/) Park H, Kingstad-Bakke B, Cleven T, Jung M, Kawaoka Y, Suresh M.Park H, et al.J Virol. 2025 Mar 18;99(3):e0086724. doi: 10.1128/jvi.00867-24. Epub 2025 Feb 3.J Virol. 2025.PMID: 39898643Free PMC article. * [ Seven decades after the Asian influenza pandemic: A historical review about immunity and vaccines against H2N2. ](https://pubmed.ncbi.nlm.nih.gov/41895046/) Tscherne A, Krammer F.Tscherne A, et al.Vaccine. 2026 Apr 19;79:128467. doi: 10.1016/j.vaccine.2026.128467. Epub 2026 Mar 26.Vaccine. 2026.PMID: 41895046Review. 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