Vaccines deploy molecules that arm a baby’s immune system to fight off serious infections, providing a layer of protection invisible to the naked eye. The image that can linger in parents’ minds, however, is often a crying infant’s flushed face, the tiny fists clenched in protest as the needle pierces a chubby thigh.
“We're very lucky, because we have so many vaccines that we can offer children now to protect them against serious disease,” said Helen Bedford, a children’s health expert at the University College London. But if each vaccine requires separate injections, this amounts to multiple jabs within a few months, which can be distressing for the baby, parents, and healthcare providers, she added.
Combining vaccines against two or more pathogens into one shot can help circumvent this problem. The earliest example of such a combination into a single product is the diphtheria, tetanus, and pertussis (DTP) vaccines, first used to vaccinate children in 1948.1 But how do scientists figure out which vaccines will pair well together and which will operate at across purposes?
“When you're vaccinating somebody, you're really stimulating [their] immune system,” said Rama Rao Amara, a vaccine development researcher at Emory University. “So, you need to be very careful about which combinations can actually work well together to avoid over- or under-stimulation.”
During the initial stages of developing a combination vaccine, researchers must consider individual vaccine antigens—such as nucleic acids, proteins, or inactivated toxins—and the immune response they provoke. Then, they can evaluate whether the immune response stimulated by one vaccine could influence the other vaccine’s ability to elicit a reaction. For instance, Amara noted that some vaccines trigger the production of cytokines which block viral replication, potentially interfering with other vaccines that use a virus for delivery, such as the Oxford-AstraZeneca Covishield vaccine.
Conversely, some vaccines enhance the efficacy of others. As COVID-19 messenger RNA (mRNA) vaccines rolled out, physicians recommended administering them alongside seasonal influenza vaccines. Researchers found that people vaccinated simultaneously against the two viral respiratory diseases often showed prolonged antibody-mediated responses against COVID-19 without compromising the immune responses against influenza.2
People’s willingness to take a COVID-19 vaccine booster when it was combined with an influenza shot, in part, prompted scientists to develop a combination COVID-19-flu vaccine.3 Preclinical studies in mice and phase 3 clinical trials in people indicated that a combined vaccine enhanced the immune response against influenza A antigens, although it decreased responses to the less-common influenza B.4,5 Amara explained that adjuvants, substances added in vaccines to improve the immune response they trigger, used with the COVID vaccine helped enhance the activity of the influenza vaccine.
Researchers have found that nucleic acid-based and protein-based vaccines enhance each other’s ability to stimulate an immune response, making them good combination vaccine candidates, explained Amara. One of the vaccines primes the immune system while the other boosts the response, resulting in enhanced and prolonged protection.6
Combination vaccines are rigorously tested for safety, but they may sometimes cause temporary pain or swelling at the injection site, and physicians may not be able to pinpoint exactly which component causes this.7 Overall, however, parents generally prefer that their children get fewer injections, said Bedford. In a survey that she conducted, a majority of the parents said they would not want their child to have more than two injections per clinic visit.8
Aside from these advantages, Bedford noted that combination vaccines can also reduce vaccine inequalities. “Particularly in remote areas where…it's difficult for parents and children to actually get to the clinic, or difficult for the immunizers to get to the families, obviously it’s going to be very beneficial, because they don't have to make repeated visits.”
- Skibinski DAG, et al. Combination vaccines. J Glob Infect Dis. 2011;3(1):63-72.
- Barouch SE, et al. Concurrent administration of COVID-19 and influenza vaccines enhances spike-specific antibody responses. Open Forum Infect Dis. 2024;11(4):ofae144.
- Tzenios N, et al. Combining influenza and COVID-19 booster vaccination strategy to improve vaccination uptake necessary for managing the health pandemic: A systematic review and meta-analysis. Vaccines. 2023;11(1):16.
- Krasilnikov I, et al. Transformative vaccination: A pentavalent shield against COVID-19 and influenza with betulin-based adjuvant for enhanced immunity. Vaccine. 2024;42(9):2191-2199.
- Anderer S. Combo COVID-19 and flu mRNA vaccine falls short of total flu protection. JAMA. 2024;332(14):1133.
- Konishi E, et al. Simultaneous immunization with DNA and protein vaccines against Japanese encephalitis or dengue synergistically increases their own abilities to induce neutralizing antibody in mice. Vaccine. 2003;21(17-18):1826-1832.
- Elliman D, Bedford H. Safety and efficacy of combination vaccines. BMJ. 2003;326(7397):995-996.
- Bedford H, Lansley M. More vaccines for children? Parents' views. Vaccine. 2007;25(45):7818-7823.
