Adult immunization initiative: Which surrogate markers should be used for vaccine efficacy?

Sir,

I read with great interest the recent article by Bhatt,¹ published in December 2025 issue of Indian Journal of Medical Research, on the young adult immunization initiative (YUVA/YAII), which articulates a compelling framework for strengthening life-course vaccination in India.¹ The author rightly underscores the alarmingly low vaccination coverage for human papillomavirus (HPV) and hepatitis B virus (HBV), leaving a substantial proportion of young adults vulnerable to preventable cancers and chronic liver disease. Young adulthood represents the most economically productive and socially dynamic segment of the population, characterized by workforce participation, mobility, and family formation. Failure to adequately protect this group from vaccine-preventable disease risks undermining national health gains and widening critical gaps in public health priorities.

Cervical cancer remains the fourth most common cancer among women globally, with India bearing nearly one-quarter of the global burden. Public awareness remains distressingly poor. In a recent study from Madhya Pradesh, none of the 295 women surveyed had knowledge of Pap smear testing or HPV vaccination.² Recently, the Government of India has launched a nationwide 90-day vaccination campaign targeting approximately 1.15 crore girls aged 14 years, with free vaccine provision at government facilities.³ Sustained awareness campaigns and integration of vaccination with adolescent and young adult health programmes will be critical to ensure the long-term success of this initiative.

HBV infection constitutes another major public health challenge and remains a leading cause of chronic liver disease and hepatocellular carcinoma. While Bhatt cites that only 22.7% of adults completing the HBV vaccination, coverage among healthcare workers (HCWs) is also suboptimal. In one Indian study, only 56.5% of HCWs were vaccinated, and merely 79% of vaccine recipients demonstrated protective anti-HBs titres (>10 IU/mL).⁴ Antibody levels were significantly lower among those vaccinated more than five years earlier, highlighting the importance of post-vaccination serological testing and booster policies where indicated. Given that 5–15% of individuals may not mount an adequate immune response (non-responders), immunization strategies must incorporate monitoring and follow-up.

In addition to HPV and HBV, consideration should be given to tuberculosis (TB) prevention in young adults. Although Bacillus Calmette–Guérin (BCG) vaccination is administered at birth under India’s Universal Immunization Programme, its protective efficacy wanes with age, with limited benefit beyond adolescence.⁵ Ongoing research into BCG revaccination has yielded mixed findings. Recent trials demonstrated no significant protection against sustained Mycobacterium tuberculosis (MTB) infection among QFT-negative adolescents,^6,7 while other analyses suggest possible reductions in respiratory infections despite no clear impact on QFT conversion.⁸ Importantly, most studies rely on QuantiFERON-TB Gold conversion as a surrogate endpoint for feasibility reasons and are often conducted in non-endemic settings, limiting generalizability.

Scar formation, frequently used as a marker of successful BCG vaccination, does not consistently correlate with protection against tuberculosis. Studies report high scar formation rates (91.4% in India and 81.4% in Sudan), yet lower corresponding PPD positivity rates.^9,10 These findings highlight the complexity of immune correlates of protection in TB. Therefore, dismissing BCG revaccination solely based on QFT conversion data warrants caution, particularly in high-burden settings such as India. In high TB burden countries, it is possible that repeated environmental exposure to MTB could have been critical to immune modulatory responses and its protective efficacy for so many years.