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Global vaccine readiness: equity-by-design in pandemic preparedness and response.

INTRODUCTION: COVID-19 showed that rapid vaccine development and roll-out, while lifesaving, can still yield large, avoidable harms when equity is not considered from the outset. Disparities in vaccine timing and coverage, especially in low-resource settings, amplified health and economic burdens, highlighting the need for preparedness frameworks that combine speed with fairness. AREAS COVERED: We synthesize evidence from literature and policy reports regarding global vaccine roll-out, focusing on avertable mortality under alternative sharing scenarios, procurement design, pooled mechanisms such as COVAX, and the role of distributed manufacturing and delivery capacity. We also examine how transparent data-sharing, effective public communication, genomic surveillance, adaptive trial designs, and modeling hubs can support more responsive and equitable vaccine deployment. Across six reflection points, we translate these lessons into practical priorities for future pandemic readiness, including strengthening healthcare infrastructure, equitable procurement, data transparency, and safeguarding public health decision-making from political and commercial distortion. EXPERT OPINION: We argue that equity-by-design is essential if vaccine innovation is to deliver equitable public health impact. This requires geographically distributed manufacturing, transparency, equity-conditioned advance purchase agreements, and pre-agreed, epidemiology-triggered allocation of vaccines. We recommend institutionalizing disaggregated reporting, standardized data-sharing, greater pathogen genomic sequencing capacity, and communication strategies that support public health protection while countering misinformation.

Humans

Comparison of the protective efficacies of the live vaccine RIT 4025 and an inactivated vaccine against a natural heterologous A/Victoria/3/75 infection.

A clinical trial was initiated in South Africa before the winter season of 1976. The study involved 253 volunteers divided into three groups of vaccinees and one control group. Two groups of vaccinees were inoculated with either one or two doses at 2 weeks' interval (10(7.2) EID 50/dose) of the RIT 4025 live recombinant strain [A/Scotland/840/74 (H3N2) serotype] and one group received one injection of an inactivated vaccine [A/Port Chalmers/1/73 (H3N2), 360 i.u., A/Scotland/840/74 (H3N2), 300 i.u. and B/Hong Kong/8/73, 300 i.u./dose]. The serum antihaemagglutinin antibody responses against the heterologous A/Victoria/3/75 strain as measured by the single radial haemolysis test were satisfactory and not statistically different in all groups of vaccinees. On the other hand, the antineuraminidase antibody response was better in the group receiving the killed vaccine. At the end of the influenza season, A/Victoria/3/75 infections were confirmed serologically. Only 12% of the infections were symptomatic. The infection rate was significantly reduced in the live vaccine groups, whereas in the killed vaccine group the percentage of infection was lower but not significantly different from that in the placebo group.

Antibodies, Viral

Trial of BCG vaccines in south India for tuberculosis prevention: first report--Tuberculosis Prevention Trial.

The protective effect of BCG vaccination is being evaluated in a controlled community trial near Madras in south India. After tuberculin and sensitin testing and radiographic and bacteriological examinations, BCG vaccines and placebo were allocated randomly to about 260 000 individuals, of whom 115 000 were definitely tuberculin negative at the time of vaccination. Intensive efforts are being made, by means of regular follow-up surveys, to identify all new cases of tuberculosis occurring in the community. This report presents the findings of the first 7(1/2) years of follow-up. Incidence of infection was high in the study population. However, incidence of bacillary disease was more frequent among initial tuberculin reactors, especially among the older persons, than among non-reactors of whom the majority were in the younger age groups. The distribution of new cases of bacillary tuberculosis among those not infected at intake did not show any evidence of a protective effect of the BCG vaccines.

Adolescent

Clinical and serologic effects of Alice strain live attenuated influenza A (H3N2) virus vaccine in an adult population.

Alice strain live attenuated influenza A (H3N2) virus was evaluated in prison volunteers. By random double blind allocation, 94 volunteers received Alice strain vaccine (AS) intranasally and 97 received placebo. The vaccine was well tolerated, and there was no serious morbidity. The number, type, duration, and severity of symptoms was not significantly different between the vaccine and placebo groups. Seventy-five per cent of vaccines with initial HAI titers less than or equal to 1:8 had 4 fold or greater titer responses on day 30. Placebo recipients experienced no titer changes. The GMT among vaccinees increased from 23.5 prior to vaccination 59.7 30 days later. Surveillance activities failed to document influenza A (H3N2) infection in the volunteer population during a 6 month follow-up period. Additional studies on the protective effects of the vaccine are required before efficacy can be determined.

Adult

Application of an economic model to the study of leprosy control costs.

The effectiveness of various control methods for reducing the incidence of leprosy have been tested over 20 years and compared with predictions made using the present current control method (early diagnosis and mass treatment). Specific vaccination of the whole population, a control measure yet to be developed, has been identified as the most effective strategy in the long run. A cost-effectiveness analysis has been carried out for three indicators, annual incidence, annual prevalence and cumulative prevalence at 20 years, using cumulative costs. The analysis indicates that specific vaccination at high levels of coverage is the most effective method for controlling incidence in the long term. Provided the cost of the vaccination campaign during the first years (roughly fourfold the funds required for carrying out the current strategy) can be supported, specific vaccination is also the most cost-effective method where a high level of effectiveness is required. Specific vaccination is still the most advantageous method if prevalence or cumulative prevalence are taken to indicate the effectiveness of leprosy control. The BCG-type of vaccination is not only less effective, it is also less cost-effective. Reducing the rate of abandonment of treatment (which in the model has been simulated by increasing the rate of resuming treatment) and earlier detection both appear as useful methods under conditions of severe budgetary constraints. Their ultimate effectiveness in terms of incidence reduction is, however, very small. As expected, segregation is costly and ineffective compared with other methods. In each simulation, the cost of treating the backlog of patients already ill or infected (incubating) at the time the control measures are initiated is high. Methods aimed at reducing transmission, such as vaccination, early treatment or segregation, have long-delayed effects on the cost even if incidence is reduced. The major cost item in these control measures is the prolonged or even life-long treatment of patients. The development of fast-acting, effective treatment is likely to be the only way to reduce the cost in the short term. Thus, in addition to research aimed at developing a vaccine for leprosy, resources should also be allocated for developing new therapeutics.

BCG Vaccine

Alice strain live attenuated influenza (H3N2) vaccin in an elderly population.

The clinical and antibody responses to Alice strain (AS) live attenuated influenza A (H3N2) vaccine and killed parenteral (KP) bivalent influenza vaccine were compared in a randomly allocated group of 150 elderly volunteers. AS recipients experienced more symptoms but these were mild and short in duration. Rhinitis occurred in 45% and pain at injection site in 25% of the AS and KP groups, respectively. Influenza A (H3N2) serum hemmaglutination inhibition titer responses were significantly higher in KP vaccinees; 95% of KP AND 60% OF AS recipients with initial titers smaller than or equal to 1:16 had fourfold or greater titer rises. KP induced significantly higher nasal neutralization titers but the proportion with fourfold or greater responses was not significantly different. Previous studies have shown poor correlations between antibody levels induced by live influenza vaccines and protection. Natural and/or challenge studies are needed before efficacy of influenza vaccines can be established.

Aged

[Vaccination of infants and schoolchildren with an influenza subunit vaccine (author's transl)].

A new influenza subunit vaccine which contains only hemagglutinin and neuraminidase antigens was investigated for reactogenicity and immunogenicity in children aged between three and 15 years. Children under six years of age received either 500 IU or 1000 IU of the commercial vaccine, those aged from six to 15 years either 1000 IU or 2000 IU. The vaccines contained the virus strains recommended by the World Health Organisation for the vaccination season 1976/77. In a double blind study the vaccinees were allocated at random to the different dosage groups. The children were examined for reactions by the vaccinating physician 24 hours after vaccination. Serum hemagglutination inhibiting antibody titers were determined before vaccination and four weeks after vaccination. In the younger age-group additional antibody determination was made two weeks after a booster injection. A very low rate of side-reactions was observed in all dosage groups. The increase of the antigen content was not associated with a higher rate of side reactions. After the first vaccination a significant rise of antibody titers could be observed in all children. After the booster injection a further increase of these antibody titers was observed. The response of the younger age group to the dosages 500 and 100 IU did not different significantly. In contrast, in the older age group the increase of the dosage from 1000 to 2000 IU was connected with a better immune response. This was especially marked in the antibody titers against the influenza B-strain virus.

Adolescent

Genetic determinants of SARS-CoV-2 and the clinical outcome of COVID-19 in Southern Bangladesh.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has had a severe impact on population health. The genetic determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in southern Bangladesh are not well understood. METHODS: This study aimed to determine the genomic variation in SARS-CoV-2 genomes that have evolved over 2 years of the pandemic in southern Bangladesh and their association with disease outcomes and virulence of this virus. We investigated demographic variables, disease outcomes of COVID-19 patients and genomic features of SARS-CoV-2. RESULTS: We observed that the disease severity was significantly higher in adults (85.3%) than in children (14.7%), because the expression of angiotensin-converting enzyme-2 (ACE-2) diminishes with ageing that causes differences in innate and adaptive immunity. The clade GK (n = 66) was remarkable between June 2021 and January 2022. Because of the mutation burden, another clade, GRA started a newly separated clustering in December 2021. The burden was significantly higher in GRA (1.5-fold) highlighted in mild symptoms of COVID-19 patients than in other clades (GH, GK, and GR). Mutations were accumulated mainly in S (22.15 mutations per segment) and ORF1ab segments. Missense (67.5%) and synonymous (18.31%) mutations were highly noticed in adult patients with mild cases rather than severe cases, especially in ORF1ab segments. Moreover, we observed many unique mutations in S protein in mild cases compared to severe, and homology modeling revealed that those might cause more folding in the protein's alpha helix and beta sheets. CONCLUSION: Our study identifies some risk factors such as age comorbidities (diabetes, hypertension, and renal disease) that are associated with severe COVID-19, providing valuable insight regarding prioritizing vaccination for high-risk individuals and allocating health care and resources. The findings of this work outlined the knowledge and mutational basis of SARS-CoV-2 for the next treatment steps. Further studies are needed to confirm the effects of structural and functional proteins of SARS-CoV-2 in detail for monitoring the emergence of new variants in future.

Adult

BCG and vole bacillus vaccines in the prevention of tuberculosis in adolescence and early adult life.

The Medical Research Council's trial of BCG and vole bacillus vaccines in the prevention of tuberculosis in Great Britain has ended after 20 years' follow-up of the 54 239 participants, who were aged 14 to 15 years when the entered the trial in 1950-2. Participants who were tuberculin positive on entry were left unvaccinated; those who were tuberculin negative were allocated at random to an unvaccinated or to a vaccinated group. The protective efficacy of each of the two vaccines, among those initially tuberculin negative, was 84% during the first five years, and gradually decreased, averaging 77% for each vaccine over the whole period. The incidence of tuberculosis decreased substantially in all groups during the trial, however, and of the total of 610 cases of tuberculosis only 27 developed between 15 and 20 years. Thus we cannot make a reliable assessment of efficacy during this final period. The prevalence and incidence of tuberculosis in Great Britain have decreased radically since this trial began. The expected benefit from large-scale BCG-vaccination of children is now far less, and may decrease further if the incidence of tuberculosis continues to decline.

Adolescent

Immunological monitoring in a controlled trial of immunotherapy in stage IIB malignant melanoma.

Fifteen patients undergoing surgery for Stage IIb malignant melanoma were randomly allocated either to a group who received a vaccine of BCG mixed with irradiated autologous melanoma cells, or a control group who received no further treatment. All patients were monitored sequentially for immunological competence and tumour-directed immunity, using a wide range of techniques, and the results were compared retrospectively with their clinical course. Three months after surgery, there was a trend towards inhibition of PHA-induced lymphocyte transformation by autologous serum in patients who developed recurrent tumour within 12 months after treatment. Serum from patients who remained tumour-free for 12 months did not inhibit stimulation of autologous lymphocytes by PHA. Apart from this test, no other immunological parameters correlated either with clinical course or with the type of treatment received.

Antibody Formation

Comparison of vaccination and treatment in controlling naturally occurring infectious bovine keratoconjunctivitis.

A vaccination study for infectious bovine keratoconjunctivitis was conducted on 108 newborn Hereford calves in the US Department of Agriculture Meat Animal Research Center cattle herd at Clay Center, Nebraska. Groups were allocated so that age of calf, sex of calf, and age of dam were equally distributed between the 54 vaccinated (group I) and the 54 nonvaccinated (group 2) control calves. The dams of both groups of calves were monitored as group 3 controls. An autogenous Moraxella bovis bacterin (formalin-killed, whole cells) was given IM at birth and at approximate intervals of 2 weeks for a total of 3 doses. Bacterial isolation rates for the cattle in groups 1, 2, and 3 during the summer were 92.6%, 92.6%, and 54.1%, respectively, and disease rates were 100%, 96.3%, and 70.6%. The rates were significantly (P less than 0.05) different between calves and cows. Vaccination of calves at birth permitted serum antibodies to develop before the calves were extensively exposed to infection; however, immunity to the disease did not develop. In a treatment study of other animals in the same herd, but in another pasture, the same criteria were used for allocation of 107 cow-calf pairs. Eye spray was applied to treated principals (group 4, 52 calves; and group 6, 53 cows) each week after examination and sample collection. Controls consisted of 54 calves (group 5) and 54 cows (group 7) that were examined and cultured bacteriologically in the same manner. The bacterial isolation and disease rates were less (P less than 0.05) in the treated calves (group 4) than in the nontreated controls (group 5). The differences in bacterial isolation rates between groups 6 and 7 were not significant, but group 6 had less (P less than 0.05) grade III lesions than did group 7. Weekly treatment appeared to be more effective in reducing the incidence of disease than did vaccination.

Age Factors

A comparison of the intradermal and subcutaneous routes of influenza vaccination with A/New Jersey/76 (swine flu) and A/Victoria/75: report of a study and review of the literature.

A trail of influenza vaccination, with use of bivalent split virus vaccine (A/New Jersey/76 and A/Victoria/75), was conducted to compare the immunogenicity and reactions when vaccine was given by the subcutaneous and intradermal routes. Volunteers 18 to 24 years old were randomized into equal groups, one group receiving 0.1 ml of vaccine intradermally and the other receiving 0.5 ml subcutaneously. For the A/Victoria vaccine, the immunogenicity of the intradermal route seemed superior; for A/New Jersey vaccine, the routes were equivalent. Adverse reactions were minimal and equivalent for both groups. In times of vaccine shortage, the intradermal route is considered to stretch vaccine supplies. Field trials of new influenza vaccines should include evaluation of the immunogenicity of and adverse reactions caused by the same vaccine given by different routes in varied dosages.

Adolescent

Adjuvant immunotherapy with bacillus Calmette-Guérin in prostatic cancer.

Ninety-two patients with histologically proved prostatic cancer were studied. Forty-six patients were treated with bacillus Calmette-Guérin (BCG) adjuvant immunotherapy, and 46 other patients, matched for stage and hormone therapy, served as controls. Survival from the time of histologic diagnosis was sixteen and one-half months longer (thirty-seven and one-half versus twenty-one months) in the BCG-treated patients. There was no mortality and only minimal morbidity. Changes in some immunologic parameters (white blood cell count, skin tests) suggest an immune response.

Aged

Chemoimmunotherapy for maintenance in acute myeloblastic leukemia.

Of 30 adult patients with acute myeloblastic leukemia, 14 achieved complete remission. Eight of these were given chemoimmunotherapy for maintenance. The immunotherapy consisted of intradermal pooled allogeneic leukemic cells (snap-frozen irradiated) and BCG vaccine given by Heaf gun, given twice in 4 weeks. The chemotherapy was given for 1 week in 4 weeks. The median duration of remission in these eight patients was 115+ weeks and the median duration of survival was 147+ weeks. The other six patients who were given chemotherapy only for maintenance had a median duration of remission of 15 weeks and a median survival of 52 weeks. The two groups cannot be compared properly, however, as allocation of patients was not random, and the chemotherapy differed significantly.

Adolescent

Successful maintenance immunotherapy by BCG of non-Hodgkin's malignant lymphomas: results of a controlled trial.

Forty-eight patients less than 65 years old, suffering non-Hodgkin's malignant lymphomas with one or more criteria of poor prognosis, were priorly placed in complete remission by an association of chemo + radio + chemotherapy. They were then randomized to receive either BCG in weekly scarifications for 3 years or no further treatment. Five patients were excluded (four after pathological reassessment); 43 are thus evaluable. There were 13 relapses out of 23 control patients and three relapses out of 20 treated patients (0.01 less than P less than 0.025). This difference is more distinct for clinical stages I and II (0.01 less than P less than 0.025) than for stages III and IV (not significant). Eight patients died in the control group whereas there was only one death in the treated group (0.025 less than P less than 0.05). These results indicate than BCG is useful in maintaining remission in about 40% of the cases and also in increasing their survival, especially in patients with clinical stages I or II.

Adolescent