Despite ongoing global efforts to combat HIV, new infections continue to rise, particularly among young people. In 2023, South Africa had more than 7 million people living with HIV (the world’s largest HIV epidemic) and 149,000 new infections (1). While a prevention method such as oral pre-exposure prophylaxis (PrEP) exists, its effectiveness depends heavily on consistent use, which remains a challenge (2). Many people struggle with the burden of taking a pill every day, while others face stigma or logistical barriers, such as having to visit clinics regularly to collect their medication.
The introduction of lenacapavir (LEN), a long-acting injectable PrEP administered only twice a year, marks an exciting new chapter in HIV prevention. LEN offers a more discreet and convenient option for individuals who struggle with daily adherence and could play a critical role in reducing new infections. Modelling suggests that if between one and two million HIV-negative people in South Africa take LEN each year, the new infections averted would be enough to end AIDS within the next 14 years (3). However, the success of LEN and other biomedical innovations depends on public confidence. As seen during the COVID-19 pandemic, misinformation can spread fast, shaping people’s perceptions of safety, side effects, and intent to use biomedical products. Early misinformation about the effects of LEN and its safety could undermine trust and discourage uptake just as rollout begins. To mitigate these risks, communication strategies must evolve alongside biomedical advances. Inoculation theory offers one promising approach.
What is inoculation theory? Inoculation theory is a psychological concept which proposes that people can resist persuasive messages or misinformation by being exposed to a small, weakened version of those messages (4). Just like vaccines build immunity by introducing a weakened virus, the ‘inoculation’ process strengthens mental defences, making people more resilient to stronger, potentially harmful influences they might encounter later (5).
Studies have shown that the protective effects of inoculation can persist over time (sometimes months), and its effects may spill over to those not directly inoculated via “post-inoculation talk,” where people share what they’ve learned with others, challenge opposing views, and reinforce their own beliefs (6). Unlike debunking, which corrects misinformation after it spreads, inoculation works as a form of pre-bunking building resistance before false information takes hold (7).
Applied to LEN, this means proactively identifying and addressing the most concerning misinformation narratives such as fears about long-term health effects or mistrust in pharmaceutical companies before they take hold. By doing so, individuals develop “mental immunity,” becoming more resilient to misinformation and better equipped to make informed decisions about new HIV prevention options.
While LEN represents a new and tangible opportunity to apply inoculation theory in HIV prevention, the concept is equally relevant to the future introduction of an HIV vaccine. A safe and effective vaccine remains one of the most critical tools needed to reach epidemic control. Yet, as seen with other vaccines, scientific breakthroughs alone do not guarantee public acceptance. Misinformation, fear, and mistrust can quickly undermine confidence and reduce uptake.
Inoculation theory can prebunk HIV vaccine misinformation and HIV misinformation in general because it does not only correct misinformation, but empowers individuals to form their own well-informed beliefs (8). When people who have been inoculated come across fake news or misinformation, they also develop the ability to dismiss the false claims, and can also educate others, making it a scalable strategy for tackling misinformation.
There are different ways to apply inoculation theory, ranging from addressing specific claims to targeting broader misinformation tactics. Inoculation has evolved from countering specific arguments (“issue-based inoculation”) to strengthening people’s ability to recognise misinformation tactics and strategies (“logic-based inoculation”) (9). For example, an issue-based inoculation approach to HIV vaccine misinformation might involve pre-emptively countering the false claim that “HIV vaccines cause HIV” by explaining that vaccines do not contain live virus and cannot cause infection. In contrast, a logic-based inoculation approach would focus on equipping individuals with the skills to recognise common misinformation tactics, such as emotional manipulation, cherry picking or reliance on false experts, helping them critically assess not just HIV vaccine myths but health misinformation more broadly.
Building on the inoculation theory, Indlela@HE2RO in collaboration with the University of Pennsylvania, Boston University and the University of Cape Town conducted the PROTECT trial, which used inoculation theory to pre-bunk HIV vaccine misinformation among adolescent girls and young women. This was a randomized controlled trial of video messages designed to counter misinformation about the HIV vaccine in South Africa. Young women aged 18–29 years were randomly divided into two groups: a control group and an intervention group. Participants in the intervention group received inoculation messages that warn them about impending HIV vaccine misinformation and explain why those claims are false or misleading. Participants in the control group received unrelated information on topics such as diabetes or nutrition, with the same length and structure as the inoculation messages. All participants, regardless of their group, read a debrief message with accurate and up-to-date information about HIV vaccines. Preliminary findings showed that the inoculation messages successfully reduced participants’ vulnerability to HIV vaccine misinformation. Those who received the inoculation messages were less likely to believe false claims about the vaccine, and this protective effect persisted three weeks later when a follow-up survey was conducted.
Inoculation theory beyond HIV? Inoculation theory has potential to improve health outcomes not only in the HIV realm but in other spaces such as child immunisations and HPV vaccines. Unlike adult vaccines, the decision on whether or not children get vaccinated or immunised rests largely on the parents or caregivers (10). Studies have shown that misinformation from social media or other sources is one contributing factor that affects parents’ and caregivers’ decisions about vaccinations (11). Therefore, using inoculation strategies to pre-bunk misinformation amongst these key influencers could be an effective way to increase vaccine confidence and uptake.
Limitations and considerations for inoculation theory Inoculation theory has limitations. It can create psychological discomfort when people are confronted with information that conflicts with their deeply held beliefs (8). Overuse of this approach may also inadvertently expose people to too much false information, which could perpetuate the same false ideologies that it was seeking to correct (12). Therefore, inoculation should not be the sole strategy for combating misinformation, but rather it must be complemented by efforts that foster open dialogue and critical thinking.
Beyond these limitations, several key considerations influence the effectiveness of inoculation theory. Just like medical vaccines protect against viruses, the success of inoculation theory against misinformation depends on the context in which it is applied. Barriers like vaccine hesitancy, low education levels, and societal mistrust must be considered (8). Likewise, misinformation interventions need to be adapted to specific social and cultural environments, much like vaccines are adapted for different populations. Another key consideration with misinformation inoculation is the duration of immunity. We must consider how long protection against misinformation lasts and explore strategies to extend its impact. This is crucial for ensuring cost-effectiveness, maximizing impact, and encouraging long-term uptake.
With advances in technology, social media and AI-generated content, misinformation is spreading faster than ever before, which means we must continually refine inoculation strategies to remain relevant and effective (13). An important way to do this is to build a strong evidence base. More research is needed to understand what works, what doesn’t, and how to scale interventions.
Reference List
- UNAIDS. Global AIDS Update 2023: Seizing the moment. Geneva: UNAIDS; 2023.
- Fisher JD, Fisher WA, Amico KR, et al. An information-motivation-behavioral skills model of adherence to antiretroviral therapy. Health Psychol. 2022;41(5):342-350.
- Jamieson L, Johnson L, Imai-Eaton JW, Meyer-Rath G. Lenacapavir: impact and cost-effectiveness of scale-up for South Africa’s HIV response. SANAC National Roundtable on Lenacapavir Access and Sustainability; 14 Oct 2025; [Johannesburg, South Africa].
- McGuire WJ. Resistance to persuasion. In: Lindzey G, Aronson E, editors. The Handbook of Social Psychology. 2nd ed. Reading (MA): Addison-Wesley; 1961. p. 191-229.
- Iverson JL, McGuire WJ, Turner L. Inoculation theory in the digital age: Resistance to misinformation. Cyberpsychol Behav Soc Netw. 2020;23(3):199-204.
- Banas JA, Rains SA. A meta-analysis of research on inoculation theory. Commun Monogr. 2010;77(3):281-311.
- Pfau M, Burgoon JK, Bichard SH, et al. The inoculation theory and its implications for persuasion. Commun Res. 2004;31(6):767-791.
- van der Linden S, Leiserowitz A, Rosenthal S, et al. Inoculating against misinformation. Science. 2017;358(6366):1147-1148
- Cameron KA, Powell EC, Woolley D, et al. The evolution of inoculation theory: A look at logic-based inoculation. Psychol Popular Media Cult. 2016;5(4):395-408
- Cohen JT, Ben-Ami D, Greco M, et al. Misinformation and vaccine hesitancy: The impact on child immunizations. J Pediatr Health. 2020;34(1):5-9.
- Freeman D, Patalay P, Baxter A, et al. Misinformation, vaccination, and public trust: The role of social media in the spread of false information. Vaccine. 2020;38(10):2363-2370.
- Lewandowsky S, Ecker UKH, Cook J. The role of misinformation in the spread of vaccine hesitancy. Science. 2012;337(6101):410-414.
- Friggeri A, Adamic LA, Eckles D, et al. Rumor cascades. In: Proceedings of the ACM SIGKDD International Conference on Knowledge Discovery and Data Mining. 2014. p. 547-556.
