Different Types of Vaccines

Vaccines have transformed human health by preventing diseases that once claimed millions of lives. The journey from early inoculation practices to today’s cutting-edge mRNA technology is a story of scientific curiosity, collaboration, and innovation. Understanding how different vaccines work helps us appreciate their role in safeguarding communities and shaping modern medicine. Let’s explore the major types of vaccine technologies, their historical breakthroughs, and the vaccines that rely on them today.

Embarking on a Journey Through the History of Vaccines

The concept of giving someone a small dose of what makes people sick to trigger immunity traces back over a thousand years. In 10th-century China, healers practiced variolation. This crude method laid the groundwork for Edward Jenner’s 1796 smallpox vaccine, (cow). Over time, scientists like Louis Pasteur expanded these ideas, developing attenuated vaccines for rabies and anthrax by weakening lab pathogens. The 20th century brought breakthroughs in cell culture, enabling vaccines for polio, measles, and rubella. Today, advances in genetic engineering and nanotechnology have revolutionized the field, exemplified by the rapid development of mRNA vaccines during the COVID-19 pandemic.

Live Attenuated Vaccines: Mimicking Natural Immunity

Live attenuated vaccines contain weakened viruses or bacteria that provoke strong immune responses without causing severe illness. Albert Sabin’s oral polio vaccine, developed in the 1960s, exemplifies this approach. By growing poliovirus in monkey kidney cells, Sabin created a strain that replicated harmlessly in the gut, training the immune system to recognize the wild virus. For example, the measles, mumps, and rubella (MMR) vaccine uses live viruses attenuated through serial cell-culture passages. These vaccines often confer lifelong immunity with one or two doses. However, they’re unsuitable for immunocompromised individuals, as even weakened pathogens pose risks.

Inactivated Vaccines: Safety Through Sterilization

Inactivated vaccines use killed pathogens, making them safer for vulnerable populations. Jonas Salk’s 1955 polio vaccine pioneered this method by treating the virus with formaldehyde. While inactivated vaccines don’t provide as durable protection as live ones, they’re crucial for diseases like rabies and hepatitis A. For example, the influenza shot—updated annually to match circulating strains—relies on inactivated viruses grown in chicken eggs or cell cultures. Modern techniques, , preserve viral structures better, enhancing immune recognition.

Toxoid Vaccines: Not Against the Pathogen, but Against the Toxins It Makes

In the late 1800s and early 1900s, some people treated with tetanus antitoxin (antibodies derived from immunized horses) faced severe allergic reactions, highlighting the need for safer solutions. By the 1920s, researchers discovered that treating tetanus toxin with formaldehyde and heat rendered it non-toxic while preserving its ability to trigger immunity. This 'toxoid' became the basis for the first commercial tetanus vaccine in 1938. Today, these toxoids are often paired with adjuvants like aluminum salts, which enhance the immune response to the vaccine.

Bacterial toxins like tetanospasmin (tetanus) or diphtheria toxin are proteins that hijack cellular processes. Toxoid vaccines expose the immune system to harmless versions of these toxins, allowing it to produce neutralizing antibodies. For example, the tetanus vaccine primes the body to recognize the toxin’s structure, enabling rapid antibody deployment if C. tetani spores later enter a wound. Crucially, toxoid vaccines prevent the toxin’s effects but don’t stop bacterial colonization—a reason why wound care remains essential even for vaccinated individuals.

Subunit Vaccines: Precision at Its Core

Subunit vaccines focus immune responses on specific pathogen components, such as proteins or polysaccharides. The hepatitis B vaccine, introduced in 1986, uses recombinant DNA technology to produce viral surface proteins in yeast cells. This approach eliminated the need for blood-derived antigens, making the vaccine safer and scalable. Another example is the human papillomavirus (HPV) vaccine, which consists of virus-like particles mimicking HPV’s outer shell. For bacterial diseases like pneumococcus, polysaccharide conjugate vaccines link sugar molecules to carrier proteins, boosting immune memory in children. These vaccines minimize side effects by excluding non-essential pathogen parts.

Viral Vector Vaccines: Borrowing Nature’s Delivery System

Viral vector vaccines employ harmless viruses to shuttle genetic instructions into cells. During the 2014–2016 Ebola outbreak, the rVSV-ZEBOV vaccine used a vesicular stomatitis virus engineered to carry an Ebola surface protein gene. When the COVID-19 pandemic struck, AstraZeneca’s vaccine adopted a chimpanzee adenovirus vector to deliver SARS-CoV-2 spike protein genes. This technology triggers robust immune responses but faces challenges: pre-existing immunity to the vector virus can reduce efficacy, and production complexities limit scalability compared to mRNA platforms.

mRNA Vaccines: A New Era of Flexibility

The COVID-19 pandemic showcased mRNA vaccines’ potential. Unlike traditional methods, mRNA vaccines instruct cells to produce viral proteins directly. mRNA, or messenger RNA, is a type of genetic material that carries instructions for protein production. ​​Katalin Karikó and Drew Weissman’s discovery of nucleoside modifications—reducing mRNA’s inflammatory potential—made this possible. Pfizer-BioNTech and Moderna’s COVID-19 vaccines encode spike proteins, prompting antibody and T-cell responses. Recent advances include self-amplifying mRNA (prolonging protein production) and thermostable lipid nanoparticles (easing storage). Researchers now explore mRNA vaccines for HIV, cancer, and seasonal flu, leveraging their rapid design and adaptability.

Why Vaccine Diversity Matters

Different technologies address unique challenges. Live vaccines excel against rapidly mutating viruses like measles, while subunit vaccines suit stable pathogens like hepatitis B. mRNA’s speed proved vital during COVID-19, but viral vectors offer durability for diseases like Ebola. Multiple platforms ensure we’re prepared for diverse threats—whether a fast-spreading pandemic or a slow-evolving endemic virus. Moreover, combining technologies (e.g., protein boosts after mRNA priming) could enhance protection against complex pathogens like HIV.

The Road Ahead: Next-Generation Innovations

Emerging technologies promise safer, broader vaccines. Nanoparticle scaffolds, like those in experimental HIV vaccines, present multiple viral proteins to elicit cross-reactive antibodies. These antibodies can recognize and neutralize a wide range of viral strains, potentially providing broader protection. CRISPR-edited live vaccines could attenuate pathogens more precisely, reducing reversion risks. Artificial intelligence accelerates antigen design, as seen in IBM-Moderna’s lipid nanoparticle optimizations. Meanwhile, 'universal' flu vaccines target conserved viral regions, aiming to eliminate annual updates.

Final Thoughts

From variolation to mRNA, vaccine technology reflects humanity’s relentless pursuit of healthier futures. Each breakthrough builds on past discoveries—Jenner’s cowpox experiments informed Pasteur’s rabies vaccine, which paved the way for modern genetic platforms. This toolkit's diversity will be our greatest asset as we confront new pathogens and climate-driven disease spread. By understanding how vaccines work, we can champion their role in saving lives and shaping a world where preventable diseases are relics of the past.

Resources and Additional Reading

1. Plotkin S. . Proc Natl Acad Sci U S A. 2014;111(34):12283-12287. doi:10.1073/pnas.1400472111
2. Jenner E. . Sampson Low; 1798.
3. Pasteur, L. .1885.
4. Enders JF, Weller TH, Robbins FC. . Science. 1949;109(2822):85-87. doi:10.1126/science.109.2822.85
5. Sabin AB. . JAMA. 1957;164(11):1216–1223. doi:10.1001/jama.1957.62980110008008
6. Salk JE. . Pediatrics. 1953;12(5):471-482.
7. Valenzuela P, Medina A, Rutter WJ, Ammerer G, Hall BD. . Nature. 1982;298(5872):347-350. doi:10.1038/298347a0
8. Zhou J, Sun XY, Stenzel DJ, Frazer IH. . Virology. 1991;185(1):251-257. doi:10.1016/0042-6822(91)90772-4
9. Henao-Restrepo AM, Camacho A, Longini IM, et al. . Lancet. 2017;389(10068):505-518. doi:10.1016/S0140-6736(16)32621-6
10. Karikó K, Buckstein M, Ni H, Weissman D. . Immunity. 2005;23(2):165-175. doi:10.1016/j.immuni.2005.06.008
11. Polack FP, Thomas SJ, Kitchin N, et al. . N Engl J Med. 2020;383(27):2603-2615. doi:10.1056/NEJMoa2034577
12. Baden LR, El Sahly HM, Essink B, et al. . N Engl J Med. 2021;384(5):403-416. doi:10.1056/NEJMoa2035389
13. Offit PA. . Smithsonian Books; 2007.
14. Orenstein WA, Ahmed R. . Proc Natl Acad Sci U S A. 2017;114(16):4031-4033. doi:10.1073/pnas.1704507114
15. World Health Organization. Vaccine Safety Basics: Learning Manual. World Health Organization; 2013. Accessed February 23, 2025. Available at:  

This article was updated on February 24, 2025. .