Rational vaccine design + correlates of protection: immunogen design, mRNA-vaccines, adjuvants, viral-vector vaccines, neutralising antibody titre, T-cell vaccine response, structural vaccinology.
Vaccinology
Rational immunogen design
Structure-guided design of immunogens that elicit broadly neutralising antibodies (bNAbs) against challenging targets (HIV / influenza /…
mRNA vaccine platform (Karikó-Weissman)
Karikó-Weissman 2005 pseudouridine-modified mRNA escapes innate-immune detection; Pardi-Hou-Karikó-Weissman 2017 LNP-mRNA platform. …
Adjuvant mechanisms (MF59 / AS04 / CpG)
Adjuvants enhance vaccine immunogenicity via depot-effect + innate-immune activation. Aluminium salts (alum) — first adjuvant 1926,…
Viral-vector vaccines (ChAdOx1 / Ad26 / VSV)
Replication-defective adenovirus encodes pathogen-antigen; elicits T-cell + antibody responses. ChAdOx1-S (Oxford-AstraZeneca COVID-19);…
Neutralising antibody titre as correlate of protection
Plotkin 2010: nAb titre is the most reliable correlate of protection for most vaccines. Threshold titres: measles 120 mIU/mL; rubella 10…
T-cell vaccine response
CD8+ cytotoxic T-cells essential against intracellular-pathogens (TB / malaria / HIV). MHC-I-restricted epitope presentation; tetramer…
Broadly neutralising antibody (bNAb)
bNAbs neutralise diverse viral strains by targeting conserved epitopes (HIV-CD4-binding-site / V3-loop / MPER / fusion-peptide; influenza…
Structural vaccinology (prefusion stabilisation)
McLellan-Graham 2013/2017: prefusion-stabilised RSV-F antigen with proline mutations preserves neutralisation-sensitive epitope. Same…
Vaccine clinical trial phases
Phase 1 (n=20-100) safety + immunogenicity dose-finding; Phase 2 (n=100-1000) expanded safety + efficacy signal; Phase 3 (n=1000-50000)…
Vaccine effectiveness real-world (test-negative design)
Test-negative design (Jackson-Nelson 2013): cases (test+) vs controls (test-) recruited from same care-seeking population — controls for…
Herd immunity threshold
Anderson-May 1985: critical-immune-fraction p_c = 1 − 1/R_0 to halt transmission. Measles R_0 ~12-18 → p_c ~92-95%. Influenza R_0…
Cold chain & vaccine stability
WHO PQS prequalification: most vaccines stable 2-8°C; mRNA-vaccines (BNT162b2 -70°C, mRNA-1273 -20°C); live-attenuated (oral-polio +2 to…
Jenner cowpox (1796)
E Jenner 1796 cowpox-smallpox vaccination; foundational vaccine; modern WHO smallpox-eradication 1980.
Salk polio (1955)
J Salk 1955 inactivated-polio vaccine; modern OPV + IPV + GPEI 99% reduction since 1988; GPEI eradication target.
Conjugate vaccine (Schneerson 1980)
R Schneerson 1980 + Robbins Hib-conjugate; modern PCV + MenACWY; T-cell-dependent polysaccharide-protein.
mRNA (Kariko-Weissman 2005)
Kariko-Weissman 2005 modified-nucleoside mRNA (Nobel 2023); foundational COVID-19 BNT162b2 + mRNA-1273.
HPV (Frazer 2006)
Frazer-zur Hausen-Lowy 2006 + HPV vaccine Gardasil + Cervarix; modern WHO 2030 cervical-cancer elimination plan.
Herd immunity (Hedrich 1933)
A Hedrich 1933 measles + 1957 fox 1980s Anderson-May; modern R0 + herd-threshold 1-1/R0 + COVID adjustments.