Nature Milestones in Vaccines

Alum adjuvant discovery and potency

The British immunologist Alexander Thomas Glenny recognized the immunostimulatory properties of aluminium salts and used alum to boost the effectiveness of the diphtheria toxoid vaccine. Read More

In 1924, tetanus toxoid — a formaldehyde-inactivated version of Clostridium tetani toxin — was produced. By 1938 tetanus toxoid was adsorbed to aluminium adjuvant to make an effective vaccine that was widely used during World War II.

First effective vaccine for whooping cough

Two vaccines were designed to combat whooping cough, one in 1939, the other in 1974. Both are imperfect, and although mostly under control, whooping cough is coming back. Read More

Two polio vaccines for defeating a paralysing scourge

Poliomyelitis has been eradicated from all but a handful of countries, all thanks to two types of vaccine developed in the 1950s — one delivering an inactivated virus through injection and an oral vaccine containing live attenuated virus. Read More

The first measles vaccines were licensed in the USA — based on an inactivated virus (Pfizer) and a live attenuated virus (Merck).

The first licensed mumps vaccine was developed by Maurice Hilleman at Merck and based on a virus sample isolated from his daughter.

The first live attenuated rubella vaccine was licensed.

Maurice Hilleman at Merck combined live attenuated measles, mumps and rubella vaccines into a single shot with no diminution in potency or increase in adverse side-effects. Rapid and widespread uptake of the vaccine led to steep drops or near elimination of these diseases in the USA.

The WHO launched the Expanded Programme on Immunization (EPI) to increase the global uptake of childhood vaccination. The initial six diseases targeted by the EPI were diphtheria, whooping cough, tetanus, measles, poliomyelitis and tuberculosis. The EPI subsequently expanded to cover vaccinations for other diseases including hepatitis B and rubella. The EPI resulted in greatly increased vaccine coverage in the developing world.

First recombinant DNA vaccine for HBV

The first vaccine against hepatitis B virus (HBV) was also the first of its kind, using recombinant DNA technology to generate virus-like particles that elicit an immune response comparable to that of the disease-causing pathogen itself. Read More

In 1977, following 10 years of a vaccination and containment programme, the last case of naturally acquired smallpox was seen in Somalia. In 1980, the World Health Assembly declared the world free of naturally occurring smallpox.

The sweet success of conjugate vaccines

The vaccine against Haemophilus influenzae type b (Hib), a major cause of bacterial meningitis and pneumonia in children, was the first of a new class of protein–polysaccharide vaccines that increase the immunogenicity of bacterial polysaccharides by conjugation to a protein carrier. Read More

Another layer of protection

Studies by Peter Aaby and colleagues in the 1980s championed the idea of nonspecific effects of vaccines, expanding on observations throughout vaccine history that some live vaccines protect against infections other than those caused by the target pathogen. Read More

Chimpanzees were protected from HIV-1 infection using a recombinant vaccine based on the HIV-1 gp120 antigen plus alum adjuvant. While not directly leading to a human vaccine, these findings offered hope that vaccination might be an effective form of prophylaxis in humans.

A vaccine to prevent HPV-related cancers

A crucial technological advance enabled the creation of human papillomavirus (HPV) virus-like particles in the lab, which were eventually used to generate the HPV vaccines that can prevent development of HPV-related cancers. Read More

Porter Warren Anderson Jr, David H. Smith, John B. Robbins and Rachel Scheerson for “Vaccine for preventing meningitis in children”.

The Global Alliance for Vaccines and Immunization (Gavi) — a public–private global health partnership — was launched to increase access to routine immunization in lower-income countries.

Vaccinology in reverse

Two landmark papers together annotated the genome of a strain of Neisseria meningitidis and used bioinformatics and biochemical tools to identify a number of novel antigens — the first case of ‘reverse vaccinology’. Read More

The quest for a vaccine against malaria

Development of the RTS,S vaccine against Plasmodium falciparum circumsporozoite protein provides the best hope so far of reaching the long-held goal of an efficient and safe vaccine against malaria. Read More

A dendritic cell cancer vaccine

A clinical trial studying vaccination of patients with prostate cancer with sipuleucel-T, a dendritic cell-based cancer vaccine personalized for each patient, led to the first approval for a cell-based cancer vaccine, although weak performance led to limited adoption. Read More

Assessing vaccine responses: you’ve got to have a system

Systems biology approaches have enabled researchers to examine vaccine responses in great detail using large datasets and mathematical modelling, revealing how the immune system responds to vaccination and providing models to predict these responses. Read More

RV144 was the first phase III clinical trial of an HIV-1 vaccine to show small signs of protective efficacy. Although the results were modest, they reinvigorated efforts to develop HIV-1 vaccines after a series of disappointing setbacks.

Sweden and Finland reported an increased incidence of the sleep disorder narcolepsy in children and adolescents (5–19 years) who had received the 2009 pandemic influenza vaccine (influenza A(H1N1)pdm09). Although it was increased, the frequency of narcolepsy was still very low (~3/100,000) and it was not seen in adults or in other regions, suggesting there may be a genetic interaction with other unknown environmental factors.

Public trust in vaccines

The issue of public confidence in vaccines is a major threat to public health, as exemplified by media coverage of a now-retracted paper by Andrew Wakefield and colleagues; in the midst of a global pandemic, addressing these concerns is more urgent than ever. Read More

Rinderpest was a serious viral disease affecting cattle. A concerted global effort led to the control of the virus and its eventual eradication in the wild — making it only the second disease to be eradicated primarily through vaccination.

Synthetic biology speeds vaccine development

Scientists downloaded the sequence of pandemic influenza virus from the internet and chemically synthesized a vaccine in record time. Read More

Coalition for Epidemic Preparedness Innovations (CEPI) — a public–private global partnership — was launched to accelerate the development of vaccines and implementation of vaccine programmes.

Dengvaxia® was the first dengue virus vaccine to be licensed and gives good protection. However, a large vaccination programme in the Philippines found that complications can develop in vaccinated children who have not been previously infected with the natural dengue virus. This seems to be related to the phenomenon of antibody-dependent enhancement. Pre-screening for dengue infection is recommended to avoid complications with the vaccine.

Individualized neoantigen vaccines

Cancer vaccines directed at mutated proteins in each patient’s tumours, manufactured via a complex and technologically demanding process, have been shown to trigger highly specific anti-tumour immune responses in patients with melanoma. Read More

The FDA approved the recombinant Ebola vaccine rVSV-ZEBOV. The vaccine was shown to provide a high level of protection during an extensive ring vaccination programme in the Democratic Republic of Congo.