New Vaccine Technologies

Nucleic Acid Vaccines - Genetic Code Shots

• Delivers genetic material (DNA or mRNA) encoding specific antigen(s) into host cells.
• Host cells transcribe (DNA) and translate (mRNA/DNA) the genetic material to produce the antigen.
• This in-situ antigen production mimics natural infection, eliciting robust cellular (T-cell) and humoral (B-cell) immunity.
• Types:
  • DNA Vaccines:
    • Plasmid DNA containing antigen gene.
    • Requires entry into nucleus for transcription.
    • Good stability; elicits strong Th1 responses.
  • mRNA Vaccines:
    • In vitro transcribed mRNA encoding antigen.
    • Direct translation in cytoplasm; no nuclear entry needed.
    • Rapid development, potent immunogenicity (e.g., COVID-19 vaccines).
    • Often encapsulated in Lipid Nanoparticles (LNPs) for delivery & stability.

⭐ mRNA vaccines (e.g., Pfizer-BioNTech, Moderna for COVID-19) are known for their rapid development and ability to elicit strong neutralizing antibody responses and T-cell immunity. They bypass the need for nuclear entry, leading to faster antigen expression compared to DNA vaccines.

• Advantages: Rapid development, scalability, safety (non-infectious, no integration risk for mRNA), induces broad immunity.
• Challenges: Delivery systems (especially for DNA), stability (mRNA more labile than DNA), potential for anti-DNA antibodies (theoretical for DNA vaccines).

Viral Vector Vaccines - Trojan Horse Tactics

• Harmless virus (vector) delivers pathogen's genetic material (DNA/RNA) into host cells. 📌 Viral Vans Deliver Genes.
• Host cells produce pathogen antigens, triggering robust immune response (cellular & humoral).
  • "Trojan Horse" delivery of antigen-coding genes.
• Vector Types:
  • Replicating: e.g., Measles, VSV. ↑Antigen, stronger immunity.
  • Non-replicating: e.g., Adenovirus (Ad26, ChAdOx1), AAV. Safer; may need boosters.
• Pros: Strong T & B-cell response; good stability.
• Cons: Pre-existing vector immunity can ↓ efficacy; manufacturing complexity.
• Examples:
  • COVID-19: J&J (Ad26), AstraZeneca (ChAdOx1).
  • Ebola: rVSV-ZEBOV.

⭐ Pre-existing adenovirus immunity can ↓ vector vaccine efficacy.

Subunit & Particle Vaccines - Protein Power-Ups

• Uses purified antigens (proteins, polysaccharides) or Virus-Like Particles (VLPs). No whole organisms.
• Pros: ↑ Safety (no infection risk), defined composition.
• Cons: Often need adjuvants; immunity may be less broad/durable.
• Examples:
  • Protein Subunit: Hepatitis B (HBsAg), Acellular pertussis.
  • Polysaccharide: Pneumococcal (PPSV23), Meningococcal. Conjugation (e.g., Hib, PCV13) vital for infant T-dependent response.
  • Virus-Like Particles (VLPs): HPV, Hepatitis B. Self-assembling viral proteins; mimic virus, highly immunogenic, non-infectious.

⭐ HPV vaccine, a VLP type, shows high efficacy by mimicking viral structure, inducing robust protective immunity against specific oncogenic HPV types.

Emerging Vaccine Tech & Adjuvants - Frontier Technologies

• Nanoparticle Vaccines: VLPs, liposomes. ↑ immunogenicity.
  • Virus-Like Particles (VLPs): Non-infectious, mimic native pathogen structures (e.g., HPV, HBV).
  • Outer Membrane Vesicles (OMVs): From Gram-negative bacteria, potent immunogens (e.g., MenB).
• Reverse Vaccinology 2.0: Genomic/proteomic antigen discovery.
• Structural Vaccinology: Structure-based rational antigen design.
• Self-amplifying RNA (saRNA): Lower dose, prolonged antigen expression than mRNA.
• Modern Adjuvants: Enhance magnitude & duration of immune response.
  • TLR Agonists: CpG ODN (TLR9), MPLA (TLR4).
  • Saponins: QS-21 (potent saponin from Quillaja saponaria).
  • Emulsions: MF59, AS03 (oil-in-water).
  • STING Agonists: Potent innate immune activation via STING.

⭐ AS04 adjuvant combines MPLA (TLR4 agonist) and alum, used in HPV (Cervarix) and HBV (Fendrix) vaccines.

High‑Yield Points - ⚡ Biggest Takeaways

• mRNA vaccines (e.g., Pfizer, Moderna) use mRNA for antigen synthesis; rapid development, no infection risk.
• Viral vector vaccines (e.g., Covishield) use a modified virus to deliver antigen genes.
• DNA vaccines (e.g., ZyCoV-D) use plasmid DNA; stable, elicit cellular and humoral immunity.
• Recombinant protein vaccines (e.g., Novavax) use purified antigens; fewer side effects.
• Virus-Like Particles (VLPs) (e.g., HPV) are non-infectious, highly immunogenic structural mimics.
• Modern adjuvants enhance immunogenicity and response duration.